Cover
Title Page
About the authors
Preface to the third edition
About the companion website
Part 1: Laboratory practice
1. 1 Safety in the chemical laboratory
  1. 1.1 Essential rules for laboratory safety
  2. 1.2 Hazardous chemicals
  3. 1.3 Disposal of hazardous waste
  4. 1.4 Accident procedures
2. 2 Glassware and equipment in the laboratory
  1. 2.1 Glass equipment
  2. 2.2 Hardware
  3. 2.3 Heating
  4. 2.4 Stirring
  5. 2.5 Vacuum pumps
  6. 2.6 The rotary evaporator
  7. 2.7 Catalytic hydrogenation
  8. 2.8 Ozonolysis
  9. 2.9 Irradiation
  10. 2.10 Compressed gases
3. 3 Organic reactions: From starting materials to pure organic product
  1. 3.1 Handling chemicals
  2. 3.2 The reaction
  3. 3.3 Purification of organic compounds
4. 4 Qualitative analysis of organic compounds
  1. 4.1 Purity
  2. 4.2 Determination of structure using chemical methods
5. 5 Spectroscopic analysis of organic compounds
  1. 5.1 Absorption spectroscopy
  2. 5.2 Infrared spectroscopy
  3. 5.3 Nuclear magnetic resonance spectroscopy
  4. 5.4 Ultraviolet spectroscopy
  5. 5.5 Mass spectrometry
6. 6 Keeping records: The laboratory notebook and chemical literature
  1. 6.1 The laboratory notebook
  2. 6.2 The research report
  3. 6.3 The chemical literature
Part 2: Experimental procedures
1. 7 Functional group interconversions
  1. 7.1 Simple transformations
  2. 7.2 Reactions of alkenes
  3. 7.3 Substitution
  4. 7.4 Reduction
  5. 7.5 Oxidation
  6. 7.6 Rearrangements
2. 8 Carbon–carbon bond‐forming reactions
  1. 8.1 Grignard and organolithium reagents
  2. 8.2 Enolate anions
  3. 8.3 Heteroatom‐stabilized carbanions
  4. 8.4 Aromatic electrophilic substitution
  5. 8.5 Pericyclic reactions
  6. 8.6 Metal‐mediated coupling reactions
3. 9 Experiments using enabling technologies
  1. 9.1 Microwave chemistry
  2. 9.2 Flow chemistry
4. 10 Projects
  1. 10.1 Natural product isolation and identification
  2. 10.2 Project in organic synthesis
  3. 10.3 Aspects of physical organic chemistry
Appendices
1. Appendix 1: Organic solvents
2. Appendix 2: Spectroscopic correlation tables
Index of chemicals
General Index
End User License Agreement

List of Tables

Chapter 03
1. Table 3.1 Heating bath fluids.
2. Table 3.2 Ice–salt mixtures.
3. Table 3.3 Solid CO₂ cooling baths.
4. Table 3.4 Some common extraction solvents.
5. Table 3.5 Some common drying agents for organic solutions.
6. Table 3.6 Suggested solvents for crystallization.
7. Table 3.7 Common drying agents for use in desiccators.
8. Table 3.8 Reporting the results of a distillation.
9. Table 3.9 Main chromatographic techniques.
10. Table 3.10 Brockmann scale for chromatographic alumina activity grades.
11. Table 3.11 Eluotropic series.
12. Table 3.12 Some useful staining systems.
13. Table 3.13 Guideline size and volume parameters for ‘flash’ chromatography.
14. Table 3.14 Guideline size and volume parameters for ‘dry flash’ chromatography.
15. Table 3.15 Commonly used stationary phases for GC.
Chapter 05
1. Table 5.1 IR correlation table.
2. Table 5.2 Properties of some deuterated NMR solvents.
3. Table 5.3 Common electronic transitions relevant to UV spectroscopy.
4. Table 5.4 Cut‐off points for solvents for UV spectroscopy.
5. Table 5.5 Common impurity peaks encountered in mass spectra.
Chapter 06
1. Table 6.1 The primary literature of organic chemistry.
Chapter 07
1. Table 7.1 Polymer‐supported reagents and their uses.
Appendix 1
1. Table A1 Properties of common laboratory solvents.
2. Table A2 Purification procedures for commonly used laboratory solvents.
Appendix 2
1. Table A3 O–H bonds.
2. Table A4 N–H bonds.
3. Table A5 C–H bonds.
4. Table A6 X ≡ Y bonds.
5. Table A7 C ═ O bonds.
6. Table A8 C ═ O bonds.
7. Table A9 Other functional groups.
8. Table A10 Approximate proton chemical shifts of methyl groups CH₃–X.
9. Table A11 Incremental rules for estimating the proton shifts of methylene and methine groups
10. Table A12 Incremental rules for estimating the chemical shifts of alkene protons.
11. Table A13 Chemical shifts of some acidic protons (very variable according to conditions).
12. Table A14 Some proton–proton coupling constants.
13. Table A15 ¹³C chemical shift ranges.
14. Table A16 Residual proton signals of common deuterated NMR solvents.
15. Table A17 Woodward rules for the UV absorption maxima of dienes.
16. Table A18 Woodward rules for the UV absorption maxima of α,β‐unsaturated ketones in ethanol.
17. Table A19 Solvent correction for UV absorption maxima of α,β‐unsaturated ketones.
18. Table A20 One‐bond cleavage processes associated with common functional groups.
19. Table A21 Common fragmentations.
20. Table A22 Common fragment ions.

List of Illustrations

Chapter 01
1. Fig. 1.1 Common hazard warning signs.
Chapter 02
1. Fig. 2.1 Glass equipment with standard‐taper ground‐glass joints (not to scale).
2. Fig. 2.2 Other standard glass equipment (not to scale).
3. Fig. 2.3 Laboratory hardware (not to scale).
4. Fig. 2.4 Right and wrong ways of using support stands, clamp holders and clamps (not to scale).
5. Fig. 2.5 (a) Heating an Erlenmeyer flask on a steam bath; (b) heating a reflux set‐up on a steam bath.
6. Fig 2.6 An aluminium heating block.
7. Fig. 2.7 Assembly for reflux using a heating mantle.
8. Fig. 2.8 A stirrer/hotplate.
9. Fig. 2.9 Using a stirrer/hotplate with an oil bath to heat a round‐bottomed flask.
10. Fig. 2.10 (a) A commercial hot‐air gun; (b) after use, the hot‐air gun should be allowed to cool in a support ring.
11. Fig. 2.11 Useful shapes of Teflon^®‐coated bar magnet.
12. Fig. 2.12 Typical overhead mechanical stirrer.
13. Fig. 2.13 Stirrer guides for closed systems: (a) Kyrides seal; (b) screw‐cap adapter (exploded view); (c) fluid‐sealed stirrer.
14. Fig. 2.14 Two useful types of stirrer: (a) propeller design for use in open vessels; (b) movable Teflon^® blade for use with tapered‐joint glassware.
15. Fig. 2.15 Schematic diagram of a water aspirator.
16. Fig. 2.16 Typical examples of water traps suitable for use with water aspirators.
17. Fig. 2.17 Schematic diagram representing the typical arrangement of a rotary vacuum pump.
18. Fig. 2.18 The ‘internal vane’ double‐action oil immersion rotary pump.
19. Fig. 2.19 Positions of the three‐way stopcock: (a) pump, manometer and apparatus connected; (b) pump isolated; (c) manometer isolated; (d) apparatus isolated.
20. Fig. 2.20 A double‐bored key two‐way stopcock.
21. Fig. 2.21 (a) Solid CO₂–acetone trap; (b) liquid nitrogen trap.
22. Fig. 2.22 (a) Typical example of a rotary evaporator; (b) exploded view of glassware showing vapour duct.
23. Fig. 2.23 A typical splash trap for use with a rotary evaporator.
24. Fig. 2.24 The procedure for continuous solvent removal using a rotary evaporator.
25. Fig. 2.25 Schematic of low‐pressure hydrogenation apparatus.
26. Fig. 2.26 Typical arrangement of apparatus for ozonolysis (not to scale).
27. Fig. 2.27 Schematic diagram of a commercial photochemical reactor.
28. Fig. 2.28 Arrangement for degassing a sample before irradiation in a commercial reactor.
29. Fig. 2.29 Apparatus for internal medium‐pressure irradiation: (a) set‐up with 1 L reaction vessel; (b) container for smaller quantities of reaction solution.
30. Fig. 2.30 Cylinders must always be strapped to a wall or a sturdy bench.
31. Fig. 2.31 A suitable trolley for transferring cylinders.
32. Fig. 2.32 Systems for delivery of liquid or gas from cylinders using a gooseneck adapter arrangement: (a) cylinder vertical, gas delivered; (b) cylinder tilted, liquid delivered.
33. Fig. 2.33 The diaphragm pressure regulator.
Chapter 03
1. Fig. 3.1 Some typical examples of modern balances (not to scale): (a) electronic four‐figure balance (weighs to the nearest 0.1 mg with a maximum of ca. 100 g); (b) single‐pan electronic balance (weighs to the nearest 0.01 g with a maximum of ca. 300 g); (c) scale pan‐type balance (weighs to the nearest 1 g with a maximum of ca. 2000 g).
2. Fig. 3.2 Transferring solids with the aid of a creased paper.
3. Fig. 3.3 The use of a glass rod to help in pouring liquids.
4. Fig. 3.4 How to flute a filter paper.
5. Fig. 3.5 Gravity filtration.
6. Fig. 3.6 Filtration of a hot solution.
7. Fig. 3.7 Suction filtration using (a) a Büchner funnel or (b) a Hirsch funnel for smaller quantities.
8. Fig. 3.8 Some typical sintered‐glass filter funnels.
9. Fig. 3.9 A filtration column can be made in a Pasteur pipette plugged with glass or cotton‐wool, covered with a thin layer of sand that supports the filter agent (Celite^®, Hyflo^® or silica gel).
10. Fig. 3.10 Some typical gas bubblers for use with inert gases.
11. Fig. 3.11 Use of a balloon to provide a temporary inert atmosphere.
12. Fig. 3.12 Flushing a syringe with inert gas from the line.
13. Fig. 3.13 Air‐sensitive reagent bottle fitted with special seal and cap.
14. Fig. 3.14 Two ways to open a reagent bottle under an inert atmosphere.
15. Fig. 3.15 (a) Withdrawing an air‐sensitive reagent by syringe; (b) transferring the reagent to an addition funnel (see also Fig. 3.22).
16. Fig. 3.16 Transfer of air‐sensitive reagents using the double‐ended needle technique.
17. Fig. 3.17 Transferring solids under an inert gas blanket.
18. Fig. 3.18 Reaction flask fitted with solid addition tube, overhead stirrer and condenser.
19. Fig. 3.19 For small‐scale reactions, a balloon filled with inert gas connected to a cut‐down syringe barrel via a short (ca. 2 cm) collar of pressure tubing and secured with an elastic band can be used to provide an inert atmosphere. Gas is introduced into the reaction vessel via a syringe needle.
20. Fig. 3.20 (a) Stirring a reaction mixture in an Erlenmeyer flask with a magnetic stirrer; (b) stirring a reaction mixture with a mechanical overhead stirrer.
21. Fig. 3.21 (a) Stirring with addition using a single‐neck flask with a Claisen adapter; (b) stirring with addition using a two‐neck flask.
22. Fig. 3.22 Stirring under an inert atmosphere with addition of an air‐sensitive reagent at low temperature.
23. Fig. 3.23 Heating a reaction mixture under reflux: (a) with a normal water condenser; (b) under an inert atmosphere; (c) with an air condenser and drying tube.
24. Fig. 3.24 Heating a reaction mixture with magnetic stirring.
25. Fig. 3.25 (a) Heating a reaction mixture to reflux during the addition of a reagent; (b) heating a stirred reaction mixture during the addition of a reagent.
26. Fig. 3.26 Heating and overhead stirring of a reaction mixture during the addition of a reagent.
27. Fig. 3.27 Apparatus for continuous removal of water from a reaction mixture using a Dean and Stark water separator (trap).
28. Fig. 3.28 Bubbling a gas through a reaction mixture.
29. Fig. 3.29 Absorbing effluent gas from a reaction mixture by trapping/scrubbing in aqueous solution.
30. Fig. 3.30 Reaction in liquid ammonia.
31. Fig. 3.31 General scheme for reaction work‐up.
32. Fig. 3.32 A separatory funnel ready for use.
33. Fig. 3.33 (a) Holding a separatory funnel during shaking; (b) holding a separatory funnel during venting. Always point the stem away from others during venting.
34. Fig. 3.34 Holding a separatory funnel whilst draining the lower layer.
35. Fig. 3.35 General outline for the separation of acidic (AH), basic (B:) and neutral (N) components of a mixture.
36. Fig. 3.36 Extraction protocol for the isolation and purification of a neutral organic compound.
37. Fig. 3.37 Extraction protocol for the isolation and purification of an acidic organic compound.
38. Fig. 3.38 Extraction protocol for the isolation and purification of a basic organic compound.
39. Fig. 3.39 Soxhlet apparatus for the extraction of solids.
40. Fig. 3.40 Plan for purification of an organic compound by crystallization.
41. Fig. 3.41 (a) Using a Pasteur pipette and cotton‐wool for filtration; (b) removing the mother liquor with a Pasteur pipette; (c) Craig tube before centrifugation; (d) Craig tube after centrifugation.
42. Fig. 3.42 Schematic plan for fractional crystallization.
43. Fig. 3.43 (a) Abderhalden drying pistol; (b) electrically heated drying pistol.
44. Fig. 3.44 Vacuum desiccator (with wire mesh safety cage).
45. Fig. 3.45 Simple phase diagram for distillation of a two‐component mixture (‐ ‐ ‐, components with markedly different bp; —, components with similar bp).
46. Fig. 3.46 Apparatus for simple distillation.
47. Fig. 3.47 Solvent still.
48. Fig. 3.48 Apparatus for fractional distillation.
49. Fig. 3.49 Some types of fractionating columns: (a) Vigreux; (b) Widmer; (c) column packed with glass beads.
50. Fig. 3.50 Nomograph for estimating the boiling point of a liquid at a particular pressure. The graph connects the boiling point at atmospheric pressure (760 mmHg) to that at reduced pressure, and a line connecting points on two of the scales intersects the third scale. For example, if the boiling point at 760 mmHg is 200 °C, the intercept shows that the boiling point at 20 mmHg pressure is about 90 °C.
51. Fig. 3.51 Apparatus for distillation under reduced pressure.
52. Fig. 3.52 (a) Bulb‐to‐bulb assembly for short‐path distillation; (b) special oven for short‐path distillation.
53. Fig. 3.53 (a) Apparatus for steam distillation; (b) a still head for steam distillation.
54. Fig. 3.54 (a) Apparatus for generating steam; (b) removing water from wet steam. Keep connecting tubes short.
55. Fig. 3.55 Alternative apparatus for steam distillation.
56. Fig. 3.56 Apparatus for sublimation using (a) a purpose‐built sublimator and (b) an improvised sublimator.
57. Fig. 3.57 Making micro‐pipettes for spotting TLC plates.
58. Fig. 3.58 A TLC plate spotted with three different amounts of sample: (a) before development; (b) after development.
59. Fig. 3.59 Simple developing tanks for TLC analysis.
60. Fig. 3.60 Developing a TLC plate.
61. Fig. 3.61 Determination of the retention factor.
62. Fig. 3.62 (a) Two compounds having similar R_f values may be indistinguishable, even when run on the same TLC plate. (b) Double spotting shows the typical ‘figure of eight’ appearance of the two closely running but different compounds.
63. Fig. 3.63 Stages in the development of a two‐dimensional chromatogram.
64. Fig. 3.64 (a) Two‐dimensional thin‐layer chromatogram of a mixture of stable components; (b) two‐dimensional chromatogram in which decomposition is occurring.
65. Fig. 3.65 Progress of multiple elution of a mixture of closely running components (note that with the later elutions, the higher running spots begin to approach each other again).
66. Fig. 3.66 Commonly encountered strangely shaped TLC spots from pure materials: (a) substance contains strongly acidic or basic groups; (b) adsorbent surface disturbed on application; (c) compound applied as a solution in a very polar solvent.
67. Fig. 3.67 Common arrangements for percolation column chromatography.
68. Fig. 3.68 Typical analysis by TLC of the fractions from a successful percolation column.
69. Fig. 3.69 Apparatus for ‘flash’ chromatography.
70. Fig. 3.70 Analytical TLC analyses of various component mixtures developed with the correct solvent combination for ‘flash’ chromatographic separation: (a) closely running components; (b) widely separated components.
71. Fig. 3.71 Apparatus for ‘dry flash’ column chromatography.
72. Fig. 3.72 Automated chromatography machine.
73. Fig. 3.73 Schematic of a typical HPLC set‐up with low‐pressure solvent mixing.
74. Fig. 3.74 Schematic diagram of the operation of an internal loop injection port for HPLC: (a) injection of sample; (b) introduction onto the column.
75. Fig. 3.75 Schematic diagram of the set‐up for GC analysis.
76. Fig. 3.76 Cross‐section through a GC injection port.
77. Fig. 3.77 (a) A typical syringe for GC analysis with a fitting for limiting plunger withdrawal; (b) technique for holding the syringe with one hand during rinsing and filling.
78. Fig. 3.78 Injecting the sample onto the column.
79. Fig. 3.79 Idealized GC trace of a sample mixture.
80. Fig. 3.80 Typical irregularities in peak shapes: (a) tailing peaks; (b) shark’s fin peaks.
81. Fig. 3.81 Typical packed‐column GC traces: (a) isothermal conditions; (b) same sample analysed with temperature programming – passage of the later components is speeded up by increasing the oven temperature.
Chapter 04
1. Fig. 4.1 Simple phase diagram for a two‐component mixture.
2. Fig. 4.2 Examples of apparatus used for capillary tube melting point determination.
3. Fig. 4.3 Sealing a melting point capillary tube.
4. Fig. 4.4 Typical changes in the appearance of a sample in the region of its melting point.
5. Fig. 4.5 Kofler block and viewing microscope.
6. Fig. 4.6 Phase diagrams for a binary mixture forming (a) a minimum boiling point azeotrope and (b) a maximum boiling point azeotrope.
7. Fig. 4.7 Small‐scale determination of boiling point.
8. Fig. 4.8 (a) Standard polarimeter sample cell; (b) jacketed cell.
9. Fig. 4.9 Solubility behaviour of common classes of organic compounds.
Chapter 05
1. Fig. 5.1 The electromagnetic spectrum: the shaded areas represent the regions of most interest to organic chemists.
2. Fig. 5.2 Schematic diagram of ATR‐IR spectroscopy.
3. Fig. 5.3 An inline IR spectrometer. In this case it is a ReactIR™.
4. Fig. 5.4 Simple IR correlation chart showing the major regions of the spectroscopic range.
5. Fig. 5.5 IR spectrum of 2‐methylcyclohexanol (cis–trans mixture).
6. Fig. 5.6 IR spectra of (a) 2‐chlorophenol and (b) salicylaldehyde.
7. Fig. 5.7 IR spectrum of cyclohexanecarboxylic acid.
8. Fig. 5.8 IR spectrum of cyclohexylamine.
9. Fig. 5.9 IR spectrum of 1‐heptyne.
10. Fig. 5.10 IR spectrum of ethyl cyanoacetate.
11. Fig. 5.11 IR spectra of (a) cyclopentanone and (b) cyclohexanone.
12. Fig. 5.12 IR spectra of (a) butanal (butyraldehyde) and (b) but‐2‐enal (crotonaldehyde).
13. Fig. 5.13 Three ways of picturing a nucleus: as a spinning, charged ball (top), a loop of current (middle) and a bar magnet (bottom).
14. Fig. 5.14 Schematic diagram of a simple NMR spectrometer.
15. Fig. 5.15 Using the ‘bar magnet’ picture, we can see that the two orientations of the nuclei relative to the static field will have different energies (top). Transitions between the resulting energy levels are responsible for the NMR absorption (bottom).
16. Fig. 5.16 NMR sample tube with typical dimensions.
17. Fig. 5.17 A convenient arrangement for filtering NMR samples.
18. Fig. 5.18 NMR tube mounted in the turbine assembly.
19. Fig. 5.19 Spinning sidebands at two different spinning speeds. With faster spinning (top) the sidebands are weaker and further from the main line.
20. Fig. 5.20 Proton NMR spectrum of benzyl acetate.
21. Fig. 5.21 Part of the proton NMR spectrum of (Z)‐3‐chloropropenoic acid, showing the splitting of each alkene signal into a doublet.
22. Fig. 5.22 The conventional presentation of a proton NMR spectrum covering the range 0–10 ppm with δ increasing from right to left.
23. Fig. 5.23 Proton NMR spectrum of 2‐methylbutane at 500 MHz.
24. Fig. 5.24 Chemical shifts of methylene protons in 1‐nitropentane at increasing distances from the electron‐withdrawing substituent.
25. Fig. 5.25 The strongly deshielded methine proton of benzaldehyde dimethylacetal.
26. Fig. 5.26 Anisotropic magnetic fields surrounding carbon–carbon single, double and triple bonds (a)–(c) and carbonyl and nitro groups (d, e). + = regions of increased shift; − = regions of decreased shift.
27. Fig. 5.27 (a) Cyclophanes and (b) 4n + 2 electron annulenes show abnormal chemical shift positions for ‘inside’ and ‘outside’ protons.
28. Fig. 5.28 Magnetic fields surrounding a benzene ring. B₀ represents the applied field and B₁ the induced field.
29. Fig. 5.29 The strongly hydrogen‐bonded phenolic proton of 2‐hydroxybenzaldehyde resonates at an anomalously high frequency. Also see Fig. 5.6(b) and its associated discussion.
30. Fig. 5.30 Proton NMR spectrum of benzyl acetate including the integral. The ratio of the peaks should be 5:2:3, and in fact is found to be 5.01:2.00:3.06 in this case.
31. Fig. 5.31 The direct, or dipolar, interaction between two protons reverses as the nuclei change from the α‐ to the β‐state.
32. Fig. 5.32 First‐order coupling. Each coupled partner has its signal split into two lines separated by J Hz.
33. Fig. 5.33 First‐order splitting patterns arising from coupling to one, two or three nuclei with distinct coupling constants J₁–J₃.
34. Fig. 5.34 The patterns arising from coupling to two or three equivalent nuclei.
35. Fig. 5.35 ‘Double of triplet’ patterns with the single coupling (a) greater than and (b) less than the sum of the couplings to the two equivalent nuclei.
36. Fig. 5.36 The observation of a ‘large’ coupling between protons usually indicates that they are in one of these two relationships.
37. Fig. 5.37 Definitions of the dihedral angle φ and valence angle θ.
38. Fig. 5.38 The relationship between vicinal coupling constants and the dihedral angle 𝜙. The values of J at 𝜙 = 0° and 𝜙 = 180° may be altered by substituent effects, but the shape of the curve remains the same.
39. Fig. 5.39 The ‘W’ arrangement of bonds most favourable for four‐bond coupling.
40. Fig. 5.40 Four‐bond coupling may also be large in strained rings.
41. Fig. 5.41 Use of homonuclear decoupling to identify coupling partners in a complex proton NMR spectrum. The lower trace is the normal spectrum, and in the top trace the doublet at δ_H 4.32 has been irradiated during the acquisition, causing one splitting to disappear from a doublet of doublets at δ_H 3.13 (marked X in the top trace).
42. Fig. 5.42 The progressive change from an AX pattern (a), through various AB quartets, to a single line for two equivalent protons (f). The spectra were simulated with J_AX = 10 Hz and δ_A – δ_B varied in the sequence (a) effectively infinite (forced X approximation), (b) 50 Hz, (c) 34 Hz, (d) 14 Hz, (e) 5 Hz and (f) 0 Hz.
43. Fig. 5.43 Simulated ABX spectra with the following parameters: J_AB = 16 Hz, J_AX = 7 Hz, J_BX = 0 Hz. δ_A – δ_B was varied in the sequence (a) 40 Hz, (b) 20 Hz, (c) 15 Hz, (d) 10 Hz and (e) 5 Hz.
44. Fig. 5.44 Protons of a methyl group are both chemically and magnetically equivalent, but the protons of 1,4‐disubstituted benzene rings are magnetically inequivalent, even though the chemical shifts of the pairs of protons (H₂, H₆) and (H₃, H₅) must be the same.
45. Fig. 5.45 Simulated AA′XX′ spectrum with J_AX = J_A′X′ = 7 Hz, J_AA′ = J_XX′ = 2.5 Hz, J_AX′ = J_A′X = 1 Hz (typical for a 1,4‐disubstituted aromatic ring).
46. Fig. 5.46 Proton NMR spectrum of 4‐(1‐methylpropyl)phenol with δ_H 7.10 [2H], δ_H 6.85 [2H], δ_H 5.20 [1H], δ_H 2.55 [1H], δ_H 1.50 [2H], δ_H 1.15 [3H] and δ_H 0.80 [3H].
47. Fig. 5.47 Proton NMR spectrum of an unknown compound (500 MHz).
48. Fig. 5.48 ¹³C NMR spectrum (with broadband proton decoupling) of myrtenol. The small signal at δ_C 77 is due to the solvent, CDCl₃; it is split into three lines because of the coupling to deuterium (I = 1).
49. Fig. 5.49 Low‐frequency expansion of the ¹³C NMR spectrum of myrtenol, with broadband (bottom) and off‐resonance (top) proton decoupling. The assignment of the peaks as singlets, doublets, etc., is mostly obvious, but even in this simple compound the off‐resonance experiment is not totally clear. The result for the two peaks near δ_C 31 is confused by the fact that their multiplets overlap in the off‐resonance experiment, and one of the two does not appear as a clean triplet owing to a large chemical shift difference between its two attached protons.
50. Fig. 5.50 Spectrum editing applied to the ¹³C NMR spectrum of myrtenol. (a) Normal ¹³C spectrum acquired with broadband proton decoupling; (b) CH carbons; (c) CH₂ carbons; (d) CH₃ carbons. Quaternary carbons (including that of the solvent CDCl₃, in which the CHCl₃ proton has been replaced by deuterium) do not appear in the edited spectra.
51. Fig. 5.51 Top ¹³C NMR, second DEPT135, third DEPT90 and bottom DEPT45 NMR spectra of the protected glycerol shown.
52. Fig. 5.52 Proton NMR spectra of the N‐methyl groups of N,N‐dimethylacetamide. As the temperature is increased, the rate of rotation about the C–N bond becomes comparable to the frequency difference between the peaks, they gradually broaden and coalesce, and eventually an averaged spectrum is obtained.
53. Fig. 5.53 D₂O exchange experiment on 2‐phenylethanol. The lower trace is the normal spectrum; D₂O was added to the sample before obtaining the upper spectrum. The peak at δ_H 1.7 has almost disappeared, and is therefore assigned to the hydroxyl resonance. The new peak at δ_H 4.7 is due to residual HDO in the D₂O (note that this signal is due to droplets of water, and is in a different place to the typical signal obtained for water dissolved in CDCl₃, which occurs at δ_H 1.57).
54. Fig. 5.54 Part of the proton NMR spectrum of a fairly complex molecule run in (a) CDCl₃, and (b) benzene‐d₆. The broad singlet at δ_H 1.57 in (a) is due to water in the CDCl₃.The large triplet in (a) is most likely to be from residual Et₂O.
55. Fig. 5.55 Normal proton NMR spectra of (E)‐ and (Z)‐methylbutenedioic acid and the corresponding nOe difference spectra obtained after pre‐irradiating the methyl group in each compound. The nOe spectra are plotted to the same absolute scale so that the size of the enhancements can be compared directly. It can be clearly seen that the nOe between the methyl group and olefinic proton in the Z‐isomer is much greater.
56. Fig. 5.56 Part of the COSY spectrum of the same compound as used for the example of homonuclear decoupling in Fig. 5.41. The connection between the doublet at δ_H 4.33 and its partner is identified by way of the cross‐peak, as indicated by the broken line drawn on the spectrum.
57. Fig. 5.57 HSQC spectrum for the protected glycerol shown.
58. Fig. 5.58 HMBC spectrum for the protected glycerol shown in Fig. 5.57.
59. Fig. 5.59 Aliasing in a one‐dimensional ¹³C NMR spectrum. The sample is butan‐2‐one.
60. Fig. 5.60 Aliasing in an HMBC spectrum. The sample is butan‐2‐one.
61. Fig. 5.61 Using NOESY to determine the difference between the structures shown: (a) sample A and (b) sample B.
62. Fig. 5.62 Energy levels of (a) ethene π‐orbitals and (b) butadiene π‐orbitals.
63. Fig. 5.63 Schematic representation of a double‐beam ultraviolet spectrometer.
64. Fig. 5.64 Standard 1 cm UV cell.
65. Fig. 5.65 UV spectrum of isophorone: (a) at a concentration of 6.2 mg per 10 mL; (b) diluted by a factor of 100.
66. Fig. 5.66 ‘Complementary’ substitution in 4‐methoxybenzaldehyde.
67. Fig. 5.67 UV spectra of 4‐nitrophenol: (a) in ethanol; (b) in ethanol with added sodium hydroxide solution.
68. Fig. 5.68 UV spectra of 4‐methoxyaniline: (a) in ethanol; (b) in ethanol with added hydrochloric acid.
69. Fig. 5.69 EI mass spectrum of chloroethane.
70. Fig. 5.70 A quadrupole mass analyser.
71. Fig. 5.71 EI mass spectrum of paracetamol (exact mass 151.0633 g mol⁻¹).
72. Fig. 5.72 ESI+ mass spectrum of paracetamol (exact mass 151.0633 g mol⁻¹, C₈H₉NO₂).
73. Fig. 5.73 MALDI mass spectrum of angiotensin I (exact mass 1296.48 g mol⁻¹, C₆₂H₈₉N₁₇O₁₄).
74. Fig. 5.74 Jet molecular separator interface for GC–MS.
75. Fig. 5.75 Loading a MALDI plate.
76. Fig. 5.76 Close‐up of a MALDI plate with the spotted sample droplets before drying.
77. Fig. 5.77 EI mass spectrum, 70 eV, of benzoic acid.
78. Fig. 5.78 Isotope abundances for carbon, silicon, sulfur, chlorine and bromine.
79. Fig. 5.79 Isotope patterns of species: (a) Br; (b) Br₂; (c) Br₃; (d) Cl; (e) Cl₂; (f) Cl₃.
80. Fig. 5.80 Mass spectrum of cyclohexylamine showing an M + 1 peak due to intermolecular self‐protonation.
81. Fig. 5.81 Illustrations of the Stephenson–Audier rule.
Chapter 06
1. Fig. 6.1 Enter all preliminary observations on the left‐hand pages of your notebook, as illustrated, and write the final report on the right‐hand pages, as shown on the opposite page.
2. Fig. 6.2 Use a tabular format for recording results of qualitative analysis investigations.
3. Fig. 6.3 A typical data sheet.
Chapter 09
1. Fig. 9.1 Microwave.
2. Fig. 9.2 Examples of (a) a monomode reactor and (b) a multimode reactor.
3. Fig. 9.3 Schematic of a flow chemistry set‐up.
4. Fig. 9.4 A representative flow unit, based on the Vapourtec E‐Series.
5. Fig. 9.5 Schematic of a typical flow reaction.
Chapter 10
1. Fig. 10.1 The free‐energy profile of competing kinetic and thermodynamic pathways.

Preface to the third edition

In its first incarnation, this book grew out of the conviction that highly developed practical skills, as well as a thorough grasp of theory, are the hallmark of a true organic chemist and that chemistry is illustrated more vividly by experiment than from a book or lecture course, when the facts can seem abstract and sterile. The original aim, therefore, was to produce a book containing safe, interesting experiments of varying complexity, together with all the associated technical instruction, which could be used in a variety of courses from the elementary to the advanced. With the goal of enthusing budding and current organic chemists, experiments were chosen to be more than just recipes for preparing a particular compound, or manipulative exercises. Rather, each experiment was associated with some important reaction, an interesting mechanism, or an underlying principle, without forgetting the practical skills to be acquired along the way. Within the constant and overriding demands for safety, the range of experiments was chosen to illustrate as many techniques and to cover as much organic chemistry as possible, in order to link up with lecture courses, and provide depth and relevance to the whole teaching programme.

So that was in the years running up to 1989 when the first edition appeared, to be followed by a second edition in 1999. Time has moved on, and this third edition of Experimental Organic Chemistry, arguably long overdue, has been born out of the recognition that much has happened in the field of organic chemistry since 1999, although the original aims espoused in the first edition still remain central.

Such progress has been made since 1989 that reactions and techniques that were once the domain of the specialist research laboratory – or indeed not even discovered when the first edition appeared – have now become commonplace in both academic and industrial environments – metal‐catalysed cross‐coupling reactions, metathesis, organocatalysis, microwave and flow chemistry are all now represented in the third edition. To this end, a new member has joined the writing team and it is doubtless that, without the professional ability, enthusiasm, verve and sheer determination to see the job finished by Dr Philippa Cranwell, this project would probably have withered and petered out. She is a very welcome addition to the team.

However, the third edition is not simply about the addition of new subject matter, but the removal of other material in recognition of the technical advances that have been made since this book was last updated. The almost immeasurable increase in computational power during the lifetime of this book has rendered much of the initial discussions of data storage and retrieval obsolete, as the power of the Internet reigns supreme and will only continue to evolve and gather force at an ever‐increasing pace. As a result, most references to hardcopy data storage and retrieval have been removed, except for that last bastion of paper – the laboratory notebook – although it is recognized that, even here, its days are numbered.

If the Internet has changed for ever the way in which we obtain and exchange information, then technological advances combined with increased computing power have radically affected the way in which experimental data are measured and interpreted. This third edition contains expanded discussions of NMR and IR spectroscopic and mass spectrometric techniques that are now routine parts of the analytical arsenal of organic chemistry, while still retaining explanations of the fundamental principles of these techniques. UV spectroscopy is retained, even though it is recognized that this technique is rarely used in the research laboratory nowadays, except as a detection method in HPLC. So why have certain aspects of spectroscopic techniques been retained in the third edition? Quite simply, the more technology takes over, the more an analytical technique becomes a ‘black box’, so much so that the chemist may forget to question and challenge; accepting mutely, the data produced. Without a fundamental understanding and appreciation of a technique being used and its pitfalls and limitations, a scientist is treading on treacherous ground when carrying out spectroscopic analysis.

Nonetheless, some techniques described in the first edition and retained in the second have simply fallen out of practice and have been removed in recognition of standard practice in teaching and research laboratories at this time. However, it is not simply older practices that have been removed. In the second edition, microscale chemical techniques were included as, during that period, these were becoming popular in student teaching programmes in many universities. They now seem to have waned in popularity worldwide, so microscale methodology and experimental procedures pertaining to student experiments have been removed, although small‐scale protocols useful at the research level have been retained.

As in the previous two editions, the book is divided into two main sections – the first surveying aspects of safety, apparatus, purification and spectroscopic techniques, and the recording and retrieval of data, and the second containing the experimental procedures and appendices. As a result of the need to include examples of more recent synthetic methodologies, the experimental section has increased to 104 experimental procedures from the 86 contained in the second edition, almost back to the 105 contained in the first edition. More importantly, the range and choice of illustrative experiments more closely reflect the experimental environment in which today’s organic chemists operate, from the fundamental to the more esoteric. As before, the experimental procedures have been further subdivided into chapters covering ‘functional group interconversions’, ‘carbon–carbon bond‐forming reactions’ and ‘projects’, but an additional chapter covering ‘enabling technologies’ – microwave and flow chemistry – has been included. We are indebted to Associate Professor Nicholas Leadbeater of the University of Connecticut for providing procedures for the flow chemistry protocols contained in this chapter, and the Moody group at the University of Nottingham for the microwave chemistry protocols. Above all, we have continued to include examples of most of the important reaction types at varying levels of experimental difficulty, so that a concerted series of experiments might be designed that is tailored to the specific teaching needs of a class or an individual student.

Safety in the laboratory is, as always, the paramount consideration when choosing or retaining an experiment, and we have attempted to minimize potential hazards by avoiding toxic materials wherever possible and by highlighting in the text any possible hazards at appropriate points of the procedure. In addition, the scale of each standard experimental procedure has been kept as small as is commensurate with the level of difficulty, to minimize any adverse consequences of an accident, in addition to lessening disposal problems and cost. Nonetheless, health and safety regulations worldwide have become complex and sometimes contradictory, so the advice always is to assess the risk and validate all procedures with the local health and safety guidelines before commencing any experimental work.

Following feedback over the past 25 years or so, the experiments in this third edition have been included for their reproducibility and all have been independently assessed for such. Each experiment is preceded by a general discussion, outlining the aims and salient features of the investigation, and is followed by a series of problems designed to emphasize the points raised in the experiment. To emphasize safety aspects, make the greatest use of time available in the teaching laboratory and encourage forward planning, apparatus, instruments and chemicals required in the experiment are listed at the beginning of the procedure, together with an estimation of the amount of time necessary to complete the experiment. Extended periods of reflux or stirring have been avoided wherever possible and long experiments have been designed so that they have clear break points at roughly 3‐hour intervals, indicated in margin notes in the procedure. The indicative degree of difficulty of each experiment is as follows:

Introductory‐level experiments requiring little previous experience.
Longer experiments with the emphasis on developing basic experimental techniques.
Experiments using more complex techniques and spectroscopic analysis.
Research level.

Data on yields and melting points, useful hints and checkers’ comments for each experiment, and guidelines for answers to all of the problems are available at the companion website: www.wiley.com/go/cranwell/EOC. Of course, almost all necessary data can be obtained from the Internet with a few clicks of a mouse or a few swipes of the finger. Nonetheless, some data tables are presented in appendices at the end of this book as we felt that these were likely to be of greatest use both to students working for their first degree and also to research workers.

In addition to those already mentioned, we would like to acknowledge others whose help has been fundamental in the production of this third edition. In alphabetical order, thanks go to Professor Matthew Almond (University of Reading), Professor Chris Braddock (Imperial College), Dr Geoff Brown (University of Reading), Professor Rainer Cramer (University of Reading), Dr Rob Haigh (University of Reading) and Associate Professor John Mckendrick (University of Reading). In addition, we reiterate our gratitude to all those individuals who gave their time, expertise and advice to assist with the production of the two preceding editions.

On the book production side, we would like to thank the Wiley team, in particular Jenny Cossham for her support, hard work and patience in making this third edition a reality, and Sarah Keegan for her dedication to seeing the project to completion.

Philippa B. Cranwell
Department of Chemistry, University of Reading, Whiteknights, Reading, UK

Laurence M. Harwood
Department of Chemistry, University of Reading, Whiteknights, Reading, UK

Christopher J. Moody
School of Chemistry, University of Nottingham, University Park, Nottingham, UK

September 2016