School of Chemistry, University of KwaZulu-Natal, Westville Campus CHEM 220W ORGANIC CHEMISTRY

Transcription

1 School of Chemistry, University of KwaZulu-Natal, Westville Campus CHEM 220W ORGANIC CHEMISTRY Course Structure The course comprises 36 lectures, 12 tutorials and 12 laboratory practical sessions. Lecturers Details are on the Chem220 website. Textbook The formal prescribed textbook for this course is P.Y. Bruice, Organic Chemistry, 2011, 6 th Edition, Pearson/Prentice Hall Note that this text will be used extensively in the course. It is thus essential that each student purchase their own copy. Other organic textbooks (Hart, Craine & Hart, Morrison & Boyd, Carey & Atkins, McMurray, Streitweiser & Heathcock, Fox & Whitesell ) and earlier editions of Bruice can also be consulted, but it is then up to the student to determine the relevant sections covered, as references will be given only for the above text. Course Assessment The Course Mark is made up as follows: Class (or DP) Mark 33%, Examination 67% The Class Mark is in turn made up as follows: 2 Class Tests 15%, 12 Laboratory Practicals 18% Class Tests There will be 2 formal class tests. Please note that the DP requirement is 100% attendance at tests. Lectures (venue: Lecture theatre L09, L Block) Attendance at lectures is compulsory and registers will be taken regularly. If you are found not to be attending lectures, you will not be granted a DP certificate to write the final examination. Lecture periods are: Monday Tuesday 2, Friday Laboratory Practicals Laboratory practical sessions will be held on Monday and Wednesday afternoons in the Synthetic Teaching Laboratories, 1 st Floor, H Block, commencing at 2.10 pm sharp, from Monday the 13 th of February. Practical manuals must be collected from the Laboratory Technician located in the laboratory in the 1 st week of lectures. Bench and locker allocations will be posted on the noticeboard outside the laboratories; anyone not on the list should please see the laboratory technician. Practical reports must be submitted to your demonstrator one week after the date of the practical. Late submissions will not be accepted. CHEM220 course outline 1

2 Closed leather shoes, laboratory coats and safety glasses must be worn in all laboratory sessions There will be NO supplementary or make up practicals. Students who miss practicals without adequate explanation will be given ZERO for that session, which may cost them their DP s (see DP requirements below). Students who are unable to attend for medical or other unavoidable reasons should give their certificates or other supporting documentation to me as soon as possible after returning to campus. Laboratory Practical Exemptions Practical exemptions may be granted to those students who are repeating a course given by this School and who attained a sufficiently high standard of work in previous years. Students wishing to apply for practical exemption must please see the School Secretary, Mrs Brenda Mostert on level 3 of the Chemistry building, and fill in an application. These will then be processed and you will be informed, before practicals begin, whether you have exemption, or are required to repeat the practical course. It is your responsibility to ensure that you either have exemption or have been allocated a bench and locker. A subminimum of 40.0% for the Class Mark, 80% attendance at Laboratory Practicals, and 100% attendance at Class Tests are DP requirements. Students who fail to attend 80% of Laboratory Practicals and 100% of Class Tests (for whatever reasons), or who fail to obtain the Class Mark subminimum will have their DPs refused, and will NOT be allowed to sit the final examination. Plagiarism Plagiarism is defined as the submission or presentation of work, in any form, which is not one's own without acknowledgement of the source(s). It is an attempt to deceive the reader that the work or ideas presented are your own, whereas, in fact they are the words/ideas of others. With regard to essays, reports and dissertations, a simple rule should be used when deciding if it is necessary to acknowledge sources. If you obtain information from an outside source, that source must be acknowledged. Another rule to follow is that any direct (verbatim) quotation must be placed in quotation marks and your wording should clearly indicate that the item is not your own work and the source immediately cited. The mere inclusion of the source in a bibliography shall not be considered sufficient acknowledgement. This applies to all work contributing to assessment, including laboratory reports and projects. All assessed work must be your own individual effort. Copying of laboratory reports, for example, is plagiarism. You may share data, where appropriate, but the calculations, answers to assignment questions and the discussion of results must be your own work. CHEM220 course outline 2

3 Work referred to from Internet sources must also be acknowledged as above, with the web address (URL) of the source included and the date accessed. Purpose of the module: This module is designed to introduce organic chemical reactions and the way in which they occur, as well as the tools used to identify the products of reactions. Learning outcomes for the module: Specific outcomes for each unit within the module are spelled out in each unit. In general, students should be able to predict reactions from starting materials as well as identify possible reagents for synthesizing target molecules. They must be able to write the mechanism of how particular organic reactions occur. They must be able to identify simple organic compounds from common analytical and spectroscopic tools. Students must be able to perform an appropriate range of laboratory techniques in organic chemistry and report on the synthesis of organic compounds, relating them to theory. Assessment criteria: Students must be able to demonstrate an understanding of organic chemical reactions by being able to write mechanisms for reactions, being able to predict products and identify reagents for target molecules in a test or examination. Students must also be able to identify simple organic compounds using spectroscopic means. Course Content Unit 1: An introduction to Nuclear Magnetic Resonance Spectroscopy (NMR) (Chapter 14) Unit 2: The chemistry of aromatic compounds (Chapters 15 and 16) Unit 3: Stereochemistry (Chapter 5) Unit 4: Substitution and elimination reactions (Chapters 8 and 9) Unit 5: Carbonyl chemistry (Chapters 17, 18 and 19) Unit 6: Reactions of Alkenes (Chapters 3 and 4) Read through the box on page 136 on the use of curved arrows before you start the course. Unit 1 NMR Spectroscopy CHEM220 course outline 3

4 After reviewing the material covered in this section you should be able to: Explain the behaviour of nuclei in the presence of an applied magnetic field Draw out a simple diagram of an NMR spectrometer Understand the effects of varying field strengths Be able to explain diamagnetic shielding effects Be able to assign the number of non-equivalent signals for a given compound Discuss the role of a reference compound and the chemical shift of a particular signal Estimate the chemical shift for a particular signal using correlation tables Clearly understand the use of signal integrals and their importance in structural elucidation Explain the effect of anisotropy on a particular signal Be able to calculate the signal splitting for a compound as well as be able to work back from a spectrum to determine the number of neighbouring protons Understand what coupling constants are and how they may be useful in determining the structure of a compound (e.g. cis/trans isomers) Given a structure one should be able to predict and draw a NMR spectrum Given a spectrum for an unknown compound be able to elucidate a plausible structure based on the information provided. One must also be able to critically assess your answer to check if it is indeed plausible Contents: Shielding, Number of non-equivalent signals, chemical shift, use of correlation tables, integration of NMR signals, anisotropic effects, signal multiplicity (first order coupling only), coupling constants and applications. Coupling in aromatic systems Introduction to NMR and nuclei effects Number of signals in the NMR spectrum Chemical shift Use of correlation tables Integration of NMR signals Anisotropic effects Splitting of signals (first order only!) Pascals triangle Examples to illustrate above concepts. Coupling constants Unit 2 Aromaticity: Reactions of Benzene and Substituted Benzenes After reviewing the material covered in this section you should: Know and understand the requirements for aromaticity & be able to apply them in determining whether or not a molecule/ion is aromatic Explain the bonding in aromatic heterocyclic molecules Give the general mechanism for electrophilic aromatic substitution Understand: o the role played by delocalisation in stabilising the intermediate carbocation o why electrophilic addition does not occur Give the mechanism for generating each of the electrophiles involved in the 5 electrophilic aromatic substitution reactions CHEM220 course outline 4

5 Understand why and be able to predict, what rearrangements will occur in a Friedel-Crafts alkylation reaction and know how to prevent this occurring, using a combination of Friedel-Crafts acylation & reduction reactions Know the starting materials, reaction conditions and products of the various substituent interconversions: o reactions of alkyl substituents o catalytic hydrogenation of double and triple bond substituents and of benzene itself o oxidation of alkyl substituents to aldehydes and carboxylic acids o reduction of nitro groups to give amines on an aromatic ring Understand the concepts of induction and resonance & how they (de)activate an aromatic ring toward electrophilic aromatic substitution and be able to draw resonance structures illustrating these concepts Understand the classification of substituents into strong, medium and weak activators and deactivators and know into which group each of the substituents fall o be able to draw resonance structures for each of these classes of substituents Understand the principles behind the effect a substituent already present on an aromatic ring has on further substitution, the connection between activation/deactivation and ortho & para/meta directing groups, why the halogens are the exceptions to this, and (of course ) draw resonance structures illustrating the above Understand the effect of substituents on reaction conditions Understand the importance that the order in which substituents are introduced onto an aromatic ring plays in the design of a particular multi-substituted aromatic ring, and how to balance the opposing effects of more than one substituent to predict the net effect Know the uses of arenediazonium salts in the syntheses of various substituted benzenes and the mechanisms involved, and the use of these salts as nucleophiles Understand why nucleophilic aromatic substitution does not readily occur, know the conditions under which it does, and the reaction conditions and mechanism involved Understand why the benzyne intermediate is needed to explain the experimental observations, & how, although it cannot be isolated, its existence is supported by trapping the intermediate Material covered in this unit: review of 1 st year/ self study o electron delocalization & bonding in benzene o nomenclature of monosubstituted benzenes, disubstituted & polysubstutited benzenes o effects of substituents on pka general reading o antiaromaticity; aromaticity to molecular orbital theory; ortho-para ratio; arenediazonium ion as electrophile; polycyclic benzenoid hydrocarbons definition of & criteria for aromaticity (Huckel rules) o selected examples (hydrocarbons, cations & anions, fused systems; heterocyclic systems) consequences of aromaticity o pka how benzene reacts & mechanism of electrophilic aromatic substitution o halogenation (Br, Cl, I) & nitration o reversible sulfonation o Friedel-Crafts alkylation; skeletal rearrangement with primary alkyl halides o Friedel-Crafts acylation; indirect alkylation by acylation-reduction reactions of aromatic substituents o oxidation & reduction reactions effects of aromatic substituents on reactivity & orientation of further substitution o substituent electron donation/withdrawal by induction &/or resonance & relationship to CHEM220 course outline 5

6 activating/deactivating ability; classification of substituents as weakly/moderately/strongly activating/deactivating effect of substituents on orientation & relationship to activating/deactivating ability o additional effects synthesis design o monosubstituted & disubstituted benzenes o trisubstituted benzenes, using arenediazonium salts nucleophilic aromatic substitution benzyne Unit 3 Stereochemistry After reviewing the material covered in this section you should: Distinguish between different kinds of isomers Use priority rules to assign cis/trans or E/Z configuration of an alkene Draw the E- or Z-isomer of a given alkene Distinguish between mirror images that are superimposable and mirror images that are not superimposable Decide whether an object is chiral or achiral Locate asymmetric carbons (stereocentres) in a molecule Define enantiomers Draw chiral molecules in tetrahedral form Draw chiral molecules in a Fischer projection Compare chiral molecules drawn in perspective formulas, Newman projection or in Fischer projection Draw the enantiomer of a given chiral compound Assign priorities to substituents around a stereogenic carbon Apply priority rules to assign R, S-configurations to stereogenic centres Know what plane-polarised light is Define an optically-active compound Draw a polarimeter Define levorotatory or dextrarotatory Calculate the specific rotation of a compound Explain what a racemic mixture is Explain the concept of an enantiomerically pure compound Calculate the optical purity of a mixture of enantiomers Calculate the enantiomeric access of a mixture of enantiomers Draw the different stereoisomers of a compound with more than one stereogenic centre Distinguish between enantiomers and diastereomers Draw the diastereomer of a given chiral compound Recognise a plane of symmetry Identify a meso compound Propose a method for the separation of two enantiomers Explain what resolution of a racemic mixture is Understand the relationship between the physical properties of pairs of enantiomers or diastereomers Understand the relationship between specific rotations of pairs of enantiomers or diastereomers Understand the relationship between the chemical properties of pairs of enantiomers or diastereomers Understand the relationship between biological properties of pairs of enantiomers or diastereomers CHEM220 course outline 6

7 Unit 4 Substitution and Elimination Reactions After reviewing the material covered in this section you should: Know how alkyl halides will react (substitution / elimination) Explain the mechanism (including the rate law for the reaction) of an S N 2 reaction in detail Predict the stereochemical outcome of an S N 2 reaction Describe the influence of the following factors on the outcome of an S N 2 reaction: o structure of substrate o the nature of the leaving group o reactivity of nucleophile o effect of solvent on reactivity of the nucleophile o influence of steric effects on nucleophilicity o concentration of nucleophile o the solvent in which the reaction is carried out Know the difference between a protic and aprotic solvent Predict the product if different nucleophiles are reacting with an alkyl halide or, vice versa, decide which nucleophile to use if a given product must be prepared from a given alkyl halide Explain the mechanism (including the rate law for the reaction) of an S N 1 reaction in detail Predict the stereochemical outcome of an S N 1 reaction Describe the influence of the following factors on the outcome of an S N 1 reaction: o structure of substrate o the nature of the leaving group o reactivity of nucleophile o the solvent in which the reaction is carried out Predict when a carbocation will rearrange and write the mechanism thereof Be cognisant of the increased stability of allylic and benzylic carbocations Be able to predict whether a specific substrate will predominantly give a S N 1 or an S N 2 reaction Explain the mechanism of an E2 reaction Predict the stability of an alkene Predict the regioselectivity of an elimination reaction and apply Zaitsev s rule Be cognisant of the stereochemical implications of an E2 reaction o (in the transition state the groups being eliminated must be in an anti-periplanar or synperiplanar conformation) Explain the mechanism of an E1 reaction, including stereochemistry and regioselectivity Predict whether a particular substrate will undergo an E1 or E2 reaction Consider the substrate and conditions of a reaction and predict what the mechanism and major product will be (Substitution - S N 1, S N 2; elimination - E1 or E2) Apply substitution and elimination reactions to the synthesis of organic compounds Unit 5 Chemistry of Carbonyl Compounds After reviewing the material covered in this section you should: Be able to identify & draw structures for the functional groups of carboxylic acids, acid anhydrides, acyl halides, esters, amides & nitriles Give the general mechanism for nucleophilic acyl substitution Understand the relationship between the basicity of a given leaving group and: o its leaving group ability CHEM220 course outline 7

8 o the pk a of its conjugate acid predict, given specific pk a values o whether or not a given substitution reaction will occur o which acid derivatives can be substituted by others o the products formed, should a reaction occur (use Table 16.1, and the reactions of NaCl, NaOAc, CH 3 OH, H 2 O and CH 3 NH 2 with each of benzoyl chloride, benzoic anhydride, methyl benzoate, benzoic acid and benzamide as specific examples) give the mechanisms involved for each of the above substitution reactions understand: o why 3 O amines do not form amides o why only one equivalent of amine is needed in the reaction with an ester, but two equivalents are required in the reactions with acyl halides & anhydrides o the differences between the mechanisms of the acid- & base-catalysed hydrolyses of esters, & why excess water is needed in the acid hydrolysis o why transesterification is a poor synthetic method for the synthesis of esters o why an excess of alcohol is required when producing esters from carboxylic acids o why a catalyst is required for amide hydrolysis understand o why aldehydes/ketones do not undergo acyl substitution, but rather nucleophilic addition or addition/substitution reactions o what factors govern the above reactions and the role of lone pair electrons o the differences in the mechanisms of reactions involving strong & weak nucleophiles o the relative reactivities of aldehydes & ketones, and where they fit in in the relative reactivities of carbonyl compounds towards nucleophiles give the mechanisms involved for each of the addition reactions understand o why addition of a 2 O amine to a ketone gives an enamine rather than a imine o the factors governing the position of a carbonyl/gem diol equilibrium o why the reaction of Grignard reagents with esters and acyl halides requires a 2:1 molar ratio, and why the reaction does not work with amides and acids o the problem involved in the reaction of LAH and esters and acyl halides, and how this can be avoided o the difference in the mechanism of the reaction of LAH with acids & amides, and why a 2:1 molar ratio is required Material covered in this unit: review of 1 st year/self study o nomenclature of acids & acid derivatives o nomenclature of aldehydes & ketones o carbonyl α-hydrogens & their acidity; keto-enol tautomerism general reading o structure of carboxylic acids & their derivatives; physical properties of carbonyl compounds; naturally occurring acids & derivatives how class 1 carbonyl compounds react: nucleophilic acyl substitution o relative reactivities of acids & their derivatives o general mechanism reactions of acids & acid derivatives o acyl halides o acid anhydrides o esters; acid catalysed ester hydrolysis; hydroxide ion promoted hydrolysis o acids CHEM220 course outline 8

9 o amides; acid catalysed amide hydrolysis o nitriles synthesis design: cyclic compound synthesis how class 2 carbonyl compounds react: nucleophilic addition o relative reactivities of aldehydes & ketones reactions of aldehydes & ketones o with carbon nucleophiles (Grignard reagents, HCN) o with hydride ion o with nitrogen nucleophiles (formation of imines, enamines & imine derivatives; Wolf-Kishner reduction) o with oxygen nucleophiles (addition of H 2 O, ROH; use as protecting groups) o with sulphur nucleophiles o with phosphonium ylides (Wittig reaction) stereochemistry of nucleophilic addition Re and Si faces synthesis design: retrosynthesis reactions of enols & enolate ions: carbonyl group α-substitution/addition o general mechanism of acid & base catalysed α-carbon substitution o halogenation of aldehydes & ketones; halogenation of acids (Hell-Volhard-Zelinsky reaction) o α-carbon alkylation o β-carbon alkylation (Michael addition) o aldol addition; mixed aldol addition; dehydration to form α,β-unsaturated aldehydes/ketones o Claisen condensation; mixed Claisen condensation o intramolecular reactions (Claisen condensation, aldol addition) Unit 6 Reactions of Alkenes After reviewing the material covered in this section you should: Know how alkenes will react Understand the thermodynamics and kinetics of a reaction Describe the mechanism of addition of a hydrogen halide to an alkene Predict the stability of a carbocation Try and predict the structure of the transition state (Hammond postulate) Describe the mechanism of the acid-catalysed addition of water to alkenes Understand the rearrangement of carbocations Explain the addition reactions of halogens to alkenes Be able to perform the addition of water to an alkene without any rearrangements (Know the mechanism of the oxymercuration reduction reaction) Be able to perform a reaction that is the equivalent of an anti-markovnikov addition of water to an alkene (Hydroboration/oxidation know mechanism) Propose a reaction for the anti-markovnikov addition of HBr to alkenes (Radical addition of HBr to alkenes know mechanism) Hydrogenation of alkenes (revision of first year self study) Propose a reagent for the syn-hydroxylation of alkenes (KMnO 4, OsO 4 ) Know how to prepare an epoxide from an alkene Predict the reactions of an epoxide Ozonolysis of alkenes (revision of first year course self study) Apply the reactions of alkenes to the synthesis of organic compounds CHEM220 course outline 9