CHEM2201: Organic Chemistry

Course Organizer: Professor A.B.Tabor

Lecturers: Professor H. C. Hailes (HCH),  Dr D. Macmillan (DM), Professor A.B.Tabor (ABT) and Dr J. Wilden (JW)

Normal prerequisite: CHEM1004 and CHEM1201

Units: 1

Course evaluation: 2011/2012 (pdf)

Moodle page: http://moodle.ucl.ac.uk/course/view.php?id=942

Course Structure

Lectures: 42

Tutorials: 16

Labs: 4 weeks of 3 days per week

Assessment

Exam: 70 % (3 hours)

Lab: 20 %

Coursework test (term 1), coursework (term 2), and tutorial work: 10%

Practical course organizer:

Dr J. Wilden

Recommended Texts

As a main textbook we recommend you use either:

  • “Organic Chemistry” J. Clayden, N. Greeves, S. Warren. 2012, Oxford UP (2nd edition) (1st edition is good as well)
  • "Organic Chemistry", J. McMurry, 8th ed, Brooks/Cole, 2004.
  • In addition, you will find: “Organic Synthesis: The Disconnection Approach: S. Warren, Wiley, to be a useful guide to retrosynthetic analysis.

Further Reading

For certain parts of the course, you may find the following books useful:

  • “Spectroscopic Methods in Organic Chemistry” D. H. Williams, I. Fleming, 6th ed, McGraw-Hill, 2007
  • “Organic Structures from Spectra” 3rd Ed. 2002, L. D. Field, S. Sternhell, and J. R. Kalman, Wiley & Sons.
  • “Core Organic Chemistry” J. Howarth, Wiley, 1998
  • “Introduction to Organic Spectroscopy” L. Harwood

Aims

The course provides an essential understanding of organic chemistry in terms of the following:

  • structure elucidation by spectroscopic means;
  • electronic structure and reactivity of carbonyl compounds;
  • synthesis and reactivity of simple molecules;
  • basic retrosynthetic analysis;
  • the use of phosphorous, sulfur, boron and silicon reagents in organic synthesis;
  • essential chemistry of heteroaromatic compounds.

Objectives

You should be able to:

  • Identify simple organic compounds by NMR spectroscopy;
  • Describe the reactivity of common functional groups;
  • Write mechanisms for all the basic types of reaction process;
  • Understand the roles of nitrogen, phosphorous, sulfur, boron and silicon in organic synthesis;
  • Design synthetic routes to a variety of cyclic and acyclic organic compounds.

Course material from the first term of CHEM2201, together with a selection of some material from CHEM1201, will form the basis of the coursework test, held in January. The content of CHEM1201 should be revised prior to attending the lectures on CHEM2201.

Parts (A) and (B) of the course run in term 1; parts (C) and (D) in term 2.

(A) Organic Synthesis I (12 lectures) ABT

REACTIVITY AND SYNTHETIC METHODS I: Revision of basic carbonyl chemistry

Reactivity of different carbonyl groups. Oxidation and reduction reactions. Addition of nucleophiles. pKa of organic compounds. Formation of acetals, imines and enamines.

REACTIVITY AND SYNTHETIC METHODS II: Enolate chemistry

Formation of enolates. Lithium enolates, enol ethers, silyl enol ethers, enamines. Halogenation and alkylation of enolates. The aldol reaction: control of reactivity and regiochemistry, specific enol equivalents, malonates. Mannich reaction. Acylation at carbon: Claisen ester condensation, Dieckmann reaction.

RETROSYNTHETIC ANALYSIS I: Concepts

Recognising functional groups (FGs). Introduction to the synthon: the concept of ‘working backwards’ (i.e. disconnecting). The concept of FG interconversion. Simple (one-group) disconnections applied to carbonyl compounds, e.g. the disconnection approach to the addition of Grignard reagents to aldehydes and ketones reviewed earlier.

RETROSYNTHETIC ANALYSIS II: 1, 3-Functionalised Compounds and Their Disconnections

Two-group disconnections: outline of general principles. The Claisen condensation analysed in a retrosynthetic fashion. Comparison with the reaction of an enolate with an aldehyde which gives a β-hydroxy carbonyl compound. Recognition that this can become an α,β-unsaturated species by simple loss of water. Examination of polarity of this species and the addition of simple nucleophiles such as amines. Masked enolate equivalents: nitroalkanes, nitriles.

REACTIVITY AND SYNTHETIC METHODS III: Conjugate addition of enolates and enols

Mechanism of conjugate addition. Factors controlling conjugate vs. direct addition. Michael addition. Synthetic methods to make α,β-unsaturated carbonyl compounds. Robinson annelation.

RETROSYNTHETIC ANALYSIS III: 1,5-Functionalised compounds and their disconnections

Analysis of conjugate addition reactions in a retrosynthetic fashion. Synthetic examples.

(B) Spectroscopy (9 lectures) HCH

1H NMR Spectroscopy

Origin of NMR, nuclear spin, magnetic field strength, instrumentation. Chemical shift scale, reference absorption, chemical shift range. Proton environments, equivalent and non-equivalent nuclei, summary of positions, integration of spectra. Spin-spin coupling, factors affecting chemical shift in detail, examples and worked problems.

Mass Spectrometry

Instrumentation and method. Isotopes and fragmentations.

13C, 19F, 31P NMR Spectroscopy

13C, 19F, 31P NMR. General features, decoupling, relaxation, summary of positions and worked problems.

Structure elucidation using IR, NMR, MS

Use of these methods to solve structures and advanced NMR and worked problems.

(C) Organic Synthesis II (12 lectures) JW

Nitrogen (2 Lectures)

The importance of amines. Their synthesis by SN2 displacement and its problems. Use of azides and phthalimides. Synthesis of amides and reduction to form amines. Reaction of amines with carbonyl compounds to form imines and enamines and the application in synthesis (control of aldol). Nitro compounds and the nitro-aldol reaction. Nitriles and their reaction with electrophiles: The Strecker synthesis of amino acids.

Phosphorus and Sulfur (2 Lectures)

Recap of the Wittig olefination and its mechanism. Recap of the phosphorus ylide. Introduction of other phosphorus reagents with similar chemistry e.g. Horner-Emmons reagents. Sulfur ylides and their use in preparing epoxides. Dithianes as protecting groups and brief look at pKa (covered later). Nucleophilicity of thiols, oxidation to sulfoxides, sulfones and sulfonic acids. Swern oxidation of primary alcohols to aldehydes and secondary alcohols to ketones.

Boron

Simple boron reducing agents and their mechanism (recap). Brief mention of other reducing agents. Structure of boranes (vacant orbital) and boronates (Tetrahedral). Hydroboration of alkenes, regiochemistry of the addition. Oxidation of boranes to alcohols. Mechanism and stereochemistry. Other reactions of organo-boranes e.g. full reduction with AcOH, halogenation.

Difunctionalised Compounds

Dihydroxylation of alkenes. Sharpless asymmetric dihydroxylation and epoxidation, value in synthesis. Acyloin and pinacol reactions.

1,2 Difunctionalised Compounds and Their Disconnections

Recap of simple 1,3 and 1,5 disconnections. Demonstration of the illogical nature of 1,2 disconnections (e.g. an α-hydroxy ketone). Strategies around this using familiar chemistry (e.g. dihydroxylation methods). Recognition of alkenes, alkynes and epoxides as sources of 1,2 difunctionalised compounds. Reactions of alkynes and how to apply their reactions in synthesis (e.g. conversion to ketones, partial reduction to alkenes)

Umpolung Methods

Introduction of Umpolung methods, particularly use of acyl anion equivalents such as dithianes and cyanohydrins. General strategies for handling illogical synthons.

Advanced Disconnections

1,4- (particularly epoxide opening by enolates) and 1,6-disconnections (e.g. ozonolysis of cyclohexene, Bayer-Villiger oxidation of cyclohexanone).

Diels-Alder Reactions

Examination of the Diels-Alder reaction and how it can be applied in a retrosynthetic sense. Some examples and general strategies in synthesis.

An emphasis on pattern recognition in target synthesis will underpin all of the material on the disconnection approach.

(D) Aromatic and Heteroaromatic Compounds (9 lectures) DM

Electrophilic Aromatic Substitution

Recap of electrophilic substitution: mechanism, typical electrophiles. Directing groups – inductive vs. resonance effects. Substitution in anilines and phenols.

Nucleophilic Aromatic Substitution

SNAr mechanism; structural requirements and typical nucleophiles.

Additional Reactions of Aromatic Compounds

The Birch Reduction

Heteroaromatic Chemistry

Five-membered heterocycles; pyrroles, furans and thiophenes. Nomenclature; structure; electrophilic substitution.

Six-membered heterocycles; pyridine. Nomenclature; structure; electrophilic and nucleophilic substitution.

Retrosynthetic analysis of pyrroles and pyridines.