Experimental Organic Chemistry, 3rd Edition

✍ Scribed by Cranwell

• Publisher: Wiley
• Year: 2017
• Tongue: English
• Leaves: 907
• Edition: 3
• Category: Library

✦ Synopsis

The definitive guide to the principles and practice of experimental organic chemistry - fully updated and now featuring more than 100 experiments

The latest edition of this popular guide to experimental organic chemistry takes students from their first day in the laboratory right through to complex research procedures. All sections have been updated to reflect new techniques, equipment and technologies, and the text has been revised with an even sharper focus on practical skills and procedures.

The first half of the book is devoted to safe laboratory practice as well as purification and analytical techniques; particularly spectroscopic analysis. The second half contains step-by-step experimental procedures, each one illustrating a basic principle, or important reaction type. Tried and tested over almost three decades, over 100 validated experiments are graded according to their complexity and all are chosen to highlight important chemical transformations and to teach key experimental skills.

New sections cover updated health and safety guidelines, additional spectroscopic techniques, electronic notebooks and record keeping, and techniques, such as semi-automated chromatography and enabling technologies such as the use of microwave and flow chemistry. New experiments include transition metal-catalysed cross-coupling, organocatalysis, asymmetric synthesis, flow chemistry, and microwave-assisted synthesis. Key aspects of this third edition include:

• Detailed descriptions of the correct use of common apparatus used in the organic laboratory
• Outlines of practical skills that all chemistry students must learn
• Highlights of aspects of health and safety in the laboratory, both in the first section and throughout the experimental procedures
• Four new sections reflecting advances in techniques and technologies, from electronic databases and information retrieval to semi-automated chromatography
• More than 100 validated experiments of graded complexity from introductory to research level
• A user-friendly experiment directory
• An instructor manual and PowerPoint slides of the figures in the book available on a companion website

A comprehensive guide to contemporary organic chemistry laboratory principles, procedures, protocols, tools and techniques, Experimental Organic Chemistry, Third Edition is both an essential laboratory textbook for students of chemistry at all levels, and a handy bench reference for experienced chemists. 

✦ Table of Contents

Table of Contents
List of Tables
List of Illustrations
Experimental Organic Chemistry
About the authors
Preface to the third edition
About the companion website
Part 1 Laboratory practice
1 Safety in the chemical laboratory
1.1 Essential rules for laboratory safety
ALWAYS
NEVER
1.1.1 Laboratory safety procedures
1.1.2 Eye protection
1.1.3 Dress
1.1.4 Equipment and apparatus
1.1.5 Handling chemicals
1.1.6 Spills
1.2 Hazardous chemicals
1.2.1 Flammable reagents
1.2.2 Explosive reagents
1.2.3 Oxidizers
1.2.4 Corrosive reagents
1.2.5 Harmful and toxic reagents
1.2.6 Suspected carcinogens
1.3.2 Water‐soluble waste
1.3.3 Organic solvents
1.4 Accident procedures
1.4.1 Fire
1.4.2 Burning chemicals
1.4.3 Burning clothing
1.4.4 Burns
1.4.5 Chemicals in the eye
1.4.6 Cuts
1.4.7 Poisoning
Further reading
2 Glassware and equipment in the laboratory
2.1 Glass equipment
2.1.1 Cleaning and drying glassware
2.2 Hardware
2.3 Heating
2.3.1 Heating baths
Water and steam baths
Oil baths and their relatives
2.3.2 Electric heating mantles
2.3.3 Stirrer/hotplates
2.3.4 Hot‐air gun
2.3.5 Microwave reactors
2.4 Stirring
2.4.1 Magnetic stirrers
2.4.2 Mechanical stirrers
2.5 Vacuum pumps
2.5.1 Water aspirators
Using a water aspirator
Water traps
2.5.2 Diaphragm pumps
2.5.3 Oil immersion rotary vacuum pumps
Pressure measurement
Air‐leak stopcocks
Cold traps
Isolation stopcocks
Operation of the rotary vacuum pump
Evacuating the system
Releasing the vacuum
Ballasting the pump
2.6 The rotary evaporator
2.6.1 The apparatus
2.6.2 Correct use of the rotary evaporator
2.7 Catalytic hydrogenation
2.7.1 Hydrogenation procedure
2.7.2 Flow Hydrogenation
Further reading
2.8 Ozonolysis
2.8.1 The apparatus
2.8.2 Ozonolysis procedure
Further reading
2.9 Irradiation
2.9.1 The photochemical reactor
2.9.2 Internal irradiation with a medium‐pressure mercury vapour lamp
Further reading
2.10 Compressed gases
2.10.1 Safe handling of gas cylinders
Gas pressure
Size and weight of cylinders
Identification of contents
Cylinders containing liquefied gas
2.10.2 The diaphragm regulator
Attaching the pressure regulator to the cylinder
Further reading
3 Organic reactions: From starting materials to pure organic product
3.1 Handling chemicals
3.1.1 Safe handling of chemicals
3.1.2 Measuring and transferring chemicals
Solids
Liquids
3.1.3 Filtration
Gravity filtration
Hot filtration
Suction filtration
3.1.4 Air‐ and moisture‐sensitive compounds: syringe techniques
Drying the apparatus
Drying the solvents
Providing an inert atmosphere
Dispensing and transferring air‐sensitive reagents
Running the reaction
Further reading
3.2 The reaction
3.2.1 Assembling the apparatus
Stirring
Stirring with addition
Stirring with addition under an inert atmosphere
Heating
Heating with stirring
Heating with addition
Heating and stirring with addition under an inert atmosphere
Continuous removal of water
Addition of gases
Reactions in liquid ammonia
3.2.2 Temperature control
3.2.3 Following the progress of a reaction
3.2.4 Reaction work‐up (isolation of the product)
How to use a separatory funnel
Preparing the separatory funnel
Transferring liquids to the separatory funnel
Shaking out
Separating the layers
Troubleshooting
Mixture is so dark that the interface is not visible
Mixture is clear but the interface is not visible
Only a single layer is visible
Insoluble material is visible at the interface
Emulsions
No product is isolated after evaporation of the organic layer
3.3 Purification of organic compounds
3.3.1 Extraction
Aqueous–organic extraction
Choice of extraction solvent
Acid–base–neutral extraction
Isolation and purification of a neutral organic compound
Isolation and purification of an acidic organic compound
Isolation and purification of a basic organic compound
Extraction of solids
Further reading
3.3.2 Solution drying
3.3.3 Crystallization
Crystallization of organic compounds
Why are the crystals pure?
Dissolution
Filtration
Crystallization and what to do if no crystals are formed
Collecting the crystals
Drying the crystals
Special crystallization techniques
Crystallization of very small quantities
Fractional crystallization
Crystals for X‐ray crystallography
Further reading
3.3.4 Drying solids
3.3.5 Distillation
Theoretical aspects
Simple distillation
Distilling solvents
Fractional distillation
Distillation under reduced pressure
Short‐path distillation
Steam distillation
Sublimation
3.3.6 Chromatography
Adsorption chromatography – a general introduction
The support or stationary phase
Elution solvents
Further reading
Thin‐layer chromatography
The TLC plate
Micro‐pipettes
Spotting the plate with sample
The developing tank
Developing the plate
Visualizing the developed plate
Retention factor (Rf)
Streaks, crescents and other strangely shaped spots
Further reading
Gravity column chromatography
The equipment
Choosing the solvent system
Packing the column
Loading the sample
Eluting the column
Disposal of the adsorbent
‘Flash’ column chromatography
The equipment
The adsorbent and solvent systems
Packing the column
Loading the sample and eluting the column
Disposal of the silica
Further reading
‘Dry flash’ column chromatography
The equipment
Choosing the solvent system
Packing the column
Loading the sample and eluting the column
Disposal of the silica
Prepacked columns
Further reading
High‐performance liquid chromatography
The equipment
Practical points for HPLC use
Further reading
Gas chromatography (gas–liquid chromatography)
The carrier gas
Packed columns and supports
Stationary phase in packed‐column GC
Capillary columns
The oven
Detector and response factors
Sample preparation
Derivatization of involatile or polar compounds
Introducing the sample onto the column
Common problems
Co‐injection as an indication of identity
Further reading
Qualitative analysis of organic compounds
4.1 Purity
4.1.1 Why bother to analyse compounds?
4.1.2 Laboratory safety
4.1.3 Criteria of purity
Melting point
Melting point range
Mixed melting point as a means of preliminary identification
Experimental procedures for recording melting points
Capillary tube method
Heated block method
Calibration of the melting point apparatus – the ‘corrected melting point’
Boiling point
Azeotropes or constant boiling point mixtures
Boiling point determination
Small‐scale determination of boiling point
Quoting bath temperatures in short‐path distillations
Specific rotation
Further reading
4.1.4 Chromatography: the problems of purity and identity versus homogeneity and a few hints
The vexed problems of absolute proof of purity and identity using chromatography
Variation of TLC solvent systems or GC temperature programmes
Variation of stationary phases
Use of different visualizing agents in TLC
4.1.5 Conclusion
4.2 Determination of structure using chemical methods
4.2.1 Qualitative analysis
Preliminary observation of general physical characteristics
Purification and determination of physical constants
5 Spectroscopic analysis of organic compounds
5.1 Absorption spectroscopy
5.2 Infrared spectroscopy
5.2.1 The spectrometer
5.2.2 Preparing the sample
5.2.3 Running the spectrum
In situ IR spectroscopy
5.2.4 Interpreting the spectrum
Initial deductions
More detailed analysis
The 4000–2500 cm−1 region
O–H (Appendix 2, Table A3)
N–H (Appendix 2, Table A4)
C–H (Appendix 2, Table A5)
The 2500–1900 cm−1 region
C≡C (Appendix 2, Table A6)
C≡N (Appendix 2, Table A6)
The 1900–1500 cm−1 region
C═O (Appendix 2, Table A7)
C═C (Appendix 2, Table A8)
The fingerprint region
Further reading
5.3 Nuclear magnetic resonance spectroscopy
5.3.1 Preparing the sample
5.3.2 Obtaining the spectrum
5.3.3 Interpreting the spectrum
Main features
Measuring chemical shifts
The meaning of chemical shifts
Measuring peak intensities
The origin of coupling
Measuring coupling constants
Typical coupling patterns
Coupling and chemical structure
Failure of the first‐order approximation
Working with 1H NMR
5.3.4 13C NMR
5.3.5 DEPT
5.3.6 Further features of NMR
Chemical exchange?
Other useful techniques
Advanced techniques
Nuclear Overhauser effect
Correlation spectroscopy (COSY)
HMQC/HSQC
HMBC
NOESY
Further reading
Introductory theory
Proton NMR
Carbon NMR
Data tables
Practical techniques
Shift reagents
Exchanging systems
Advanced techniques
5.4 Ultraviolet spectroscopy
5.4.1 The instrument
5.4.2 Preparing the sample
Cells
Concentration
Solvent
Making up the sample
5.4.3 Running the spectrum
5.4.4 Interpreting the spectrum
Further reading
5.5 Mass spectrometry
5.5.1 The instrument
The ionization source
The mass analyser
The detector
Additional techniques
5.5.2 Preparing the sample
Avoiding contamination
5.5.3 Running the spectrum
Sample submission
Recording and calibrating spectra
5.5.4 Interpretation of spectra
Isotopes
The molecular ion
The nitrogen rule
Common fragmentation pathways
High‐resolution mass measurement
Further reading
Further experimental aspects
Mass spectrometry
6 Keeping records: The laboratory notebook and chemical literature
6.1 The laboratory notebook
6.1.1 Style and layout
6.1.2 The e‐notebook
6.1.3 Reporting spectroscopic and microanalytical data
Infrared spectra
Nuclear magnetic resonance spectra
Mass spectra
Ultraviolet spectra
6.1.4 Elemental analysis
6.1.5 Calculating yields
6.1.6 Data sheets
6.1.7 References
6.2 The research report
Further reading
6.3 The chemical literature
6.3.1 Primary literature
6.3.2 Review literature
6.3.3 Major reference works
6.3.4 Conclusion
Further reading
Part 2 Experimental procedures
Introduction
List of experiments
Experiments that can be taken in sequence
Experiments that can be used to compare directly different techniques for undertaking a reaction
Experiments that illustrate particular techniques
7 Functional group interconversions
7.1 Simple transformations
Experiment 1 Preparation of 3‐methyl‐1‐butyl ethanoate (isoamyl acetate) (pear essence)
Procedure
Problems
Experiment 2 Preparation of s‐butyl but‐2‐enoate (s‐butyl crotonate)
Procedure
Problems
Experiment 3 Preparation of N‐methylcyclohexanecarboxamide
Procedure
Problems
Further reading
Experiment 4 Protection of ketones as ethylene acetals (1,3‐dioxolanes)
Procedure
Problems
Further reading
Experiment 5 Preparation of (E)‐benzaldoxime
Procedure
Problems
Further reading
Experiment 6 Preparation of 4‐bromoaniline (p‐bromoaniline)
Procedure
1 Preparation of N‐phenylethanamide (acetanilide)
2 Preparation of N ‐(4‐bromophenyl)ethanamide (p‐bromoacetanilide)
3 Preparation of 4‐bromoaniline
Problems
7.2 Reactions of alkenes
Experiment 7 Stereospecific preparation of trans‐cyclohexane‐1,2‐diol via bromohydrin and epoxide formation
Procedure
1 Preparation of cyclohexene oxide
2 Preparation of trans‐cyclohexane‐1,2‐diol
Problems
Further reading
7.2.1 Stereospecific syntheses of cis‐1,2‐diols from alkenes
Experiment 8 Preparation of cis‐cyclohexane‐1,2‐diol by the Woodward method
Procedure
1 Preparation of cis‐2‐acetoxycyclohexanol
2 Preparation of cis‐cyclohexane‐1,2‐diol
Problems
Further reading
Experiment 9 Asymmetric dihydroxylation of trans‐1,2‐diphenylethene (trans‐stilbene)
Procedure
Problems
Further reading
Experiment 10 Preparation of ethyl (E)‐3‐methyl‐3‐phenylglycidate
Procedure
Problems
Further reading
Experiment 11 Peracid epoxidation of cholesterol: 3β‐hydroxy‐5α,6α‐epoxycholestane
Experiment 11 Peracid epoxidation of cholesterol: 3β‐hydroxy‐5α,6α‐epoxycholestane
Procedure
Problems
Further reading
Experiment 12 The Sharpless epoxidation: asymmetric epoxidation of (E)‐3,7‐dimethyl‐2,6‐octadien‐1‐ol (geraniol)
Experiment 12 The Sharpless epoxidation: asymmetric epoxidation of (E)‐3,7‐dimethyl‐2,6‐octadien‐1‐ol (geraniol)
Procedure
1 Preparatory operations
2 Preparation of (2S,3S)‐epoxygeraniol
Problems
Further reading
Experiment 13 Hydration of alkenes by hydroboration–oxidation: preparation of octan‐1‐ol from 1‐octene
Procedure
Problems
Further reading
Experiment 14 Preparation of 7‐trichloromethyl‐8‐bromo‐Δ1‐p‐menthane by free‐radical addition of bromotrichloromethane to β‐pinene
Experiment 14 Preparation of 7‐trichloromethyl‐8‐bromo‐Δ1‐p‐menthane by free‐radical addition of bromotrichloromethane to β‐pinene
Procedure
Problems
Further reading
7.3 Substitution
Experiment 15 Preparation of 1‐iodobutane by SN2 displacement of bromide: the Finkelstein reaction
Procedure
Problems
7.3.1 Free‐radical substitution
Experiment 16 Preparation of 4‐bromomethylbenzoic acid by radical substitution and conversion to 4‐methoxymethylbenzoic acid by nucleophilic substitution
Procedure
1 Preparation of 4‐bromomethylbenzoic acid
2 Preparation of 4‐methoxymethylbenzoic acid (optional)
Problems
Further reading
7.4 Reduction
7.4.1 Reduction with hydride transfer reagents
Experiment 17 Preparation of methyl diantilis
Polymer‐supported reagents
Procedure
1 Preparation of 3‐ethoxy‐4‐hydroxybenzyl alcohol
2 Preparation of methyl diantilis
Problems
Further reading
Experiment 18 Reduction of benzophenone with sodium borohydride: preparation of diphenylmethanol
Procedure
Problems
Further reading
Experiment 19 Reduction of 4‐t‐butylcyclohexanone with sodium borohydride
Procedure
1 Preparation of cis‐ and trans‐4‐t‐butylcyclohexanol
2 GC analysis
Problems
Further reading
Experiment 20 Stereospecific reduction of benzoin with sodium borohydride: determination of the stereochemistry by 1H NMR spectroscopy
Procedure
1 Preparation of 1,2‐diphenylethane‐1,2‐diol
2 Preparation of acetonide derivative (2,2‐dimethyl‐4,5‐diphenyl‐1,3‐dioxolane)
Problems
Further reading
Experiment 21 Chemoselectivity in the reduction of 3‐nitroacetophenone
Procedure
1 Reduction using tin and hydrochloric acid: 3‐aminoacetophenone
Reduction using sodium borohydride: 1‐(3‐nitrophenyl)ethanol
Problems
Further reading
Experiment 22 Reduction of diphenylacetic acid with lithium aluminium hydride
Procedure
Problems
Further reading
Experiment 23 Reduction of N‐methylcyclohexanecarboxamide with lithium aluminium hydride: N‐methylcyclohexylmethylamine
Procedure
Problems
Further reading
Experiment 24 Reduction of butyrolactone with diisobutylaluminium hydride and estimation by 1H NMR of the relative proportions of 4‐hydroxybutanal and its cyclic isomer, 2‐hydroxytetrahydrofuran, in the product mixture
Procedure
Problems
Further reading
7.4.2 Reduction of aldehyde or ketone carbonyl groups to methylene groups
Experiment 25 Wolff–Kishner reduction of propiophenone to n‐propylbenzene
Procedure
Problems
Further reading
Experiment 26 Preparation of ethylbenzene
1 Preparation of carbomethoxyhydrazone
2 Preparation of carbomethoxyhydrazone
Problems
Further reading
7.4.3 Catalytic hydrogenation
Experiment 27 Preparation of Adams’ catalyst and the heterogeneous hydrogenation of cholesterol
Procedure
1 Preparation of Adams’ catalyst
2 Hydrogenation of cholesterol
Problems
Further reading
Experiment 28 Preparation of Wilkinson’s catalyst and its use in the selective homogeneous reduction of carvone to 7,8‐dihydrocarvone
Procedure
1 Preparation of Wilkinson’s catalyst
2. Selective reduction of carvone
Problems
Further reading
7.4.4 Dissolving metal reduction
Experiment 29 Birch reduction of 1,2‐dimethylbenzene (o‐xylene): 1,2‐dimethyl‐1,4‐cyclohexadiene
Experiment 29 Birch reduction of 1,2‐dimethylbenzene (o‐xylene): 1,2‐dimethyl‐1,4‐cyclohexadiene
Procedure
Problems
Further reading
7.4.5 Biological reduction
Experiment 30 Reduction of ethyl 3‐oxobutanoate using baker’s yeast; asymmetric synthesis of (S)‐ethyl 3‐hydroxybutanoate
Procedure
Problems
Further reading
7.5 Oxidation
7.5.1 Oxidation of alcohols
Experiment 31 Oxidation of 2‐methylcyclohexanol to 2‐methylcyclohexanone using aqueous chromic acid
Experiment 31 Oxidation of 2‐methylcyclohexanol to 2‐methylcyclohexanone using aqueous chromic acid
Procedure
Problems
Further reading
Experiment 32 Oxidation of menthol to menthone using aqueous chromic acid
Procedure
1. Oxidation of (–)‐menthol
2. GC analysis
Problems
Further reading
Experiment 33 Oxidation of 1‐heptanol to heptanal using pyridinium chlorochromate
Procedure
1 Preparation of pyridinium chlorochromate (PCC) 1
2 Oxidation of 1‐heptanol with PCC
Problem
Further reading
Experiment 34 Preparation of ‘active’ manganese dioxide and the oxidation of (E)‐3‐phenyl‐2‐propenol (cinnamyl alcohol) to (E)‐3‐phenyl‐2‐propenal (cinnamaldehyde)
Procedure
1 Preparation of activated manganese dioxide on carbon
2 Preparation of (E)‐3‐phenyl‐2‐propenal (cinnamaldehyde)
Problems
Further reading
Experiment 35 Organic supported reagents: oxidations with silver(I) carbonate on Celite® (Fetizon’s reagent)
Procedure
1 Preparation of silver carbonate on Celite® (Fetizon’s reagent)
2 Oxidation of 2‐furanmethanol
3 Conversion of hexane‐1,6‐diol to caprolactone
Problems
Further reading
7.6 Rearrangements
Experiment 36 Preparation of 2‐aminobenzoic acid (anthranilic acid) by Hofmann rearrangement of phthalimide
Procedure
Problems
Further reading
Experiment 37 Investigation into the stereoselectivity of the Beckmann rearrangement of the oxime derived from 4‐bromoacetophenone
Procedure
1 Conversion of 4‐bromoacetophenone to the oxime
2 Beckmann rearrangement of the oxime
3 Hydrolysis of the amide
Problems
Further reading
8 Carbon–carbon bond‐forming reactions
8.1 Grignard and organolithium reagents
Experiment 38 Grignard reagents: addition of phenylmagnesium bromide to ethyl 3‐oxobutanoate ethylene acetal
Procedure
1 Preparation and reaction of the Grignard reagent
2 Hydrolysis of the acetal: 4,4‐diphenylbut‐3‐en‐2‐one (optional)
Problems
Further reading
Experiment 39 Preparation of isophorone
Procedure
Problem
Experiment 40 Conjugate addition of a Grignard reagent to s‐butyl but‐2‐enoate (s‐butyl crotonate): preparation and saponification of s‐butyl 3‐methylheptanoate
Experiment 40 Conjugate addition of a Grignard reagent to s‐butyl but‐2‐enoate (s‐butyl crotonate): preparation and saponification of s‐butyl 3‐methylheptanoate
Procedure
FUME HOOD
1 Preparation of s‐butyl 3‐methylheptanoate
Problems
Further reading
Experiment 41 Acetylide anions: preparation of ethyl phenylpropynoate (ethyl phenylpropiolate)
Procedure
FUME HOOD
Problems
Further reading
Experiment 42 Generation and estimation of a solution of t‐butyllithium and preparation of the highly branched alcohol tri‐t‐butylcarbinol [3‐(1,1‐dimethyl)ethyl‐2,2,4,4‐tetramethylpentan‐3‐ol]
Procedure
FUME HOOD
1 Preparation of t‐butyllithium
2 Titration of t‐butyllithium solution
3 Preparation of tri‐t‐butylcarbinol
Problems
Further reading
8.2 Enolate anions
8.2.1 Additions of enolate anions to carbonyl compounds
Further reading
8.2.2 The Knoevenagel reaction
Experiment 43 Preparation of (E)‐3‐phenylpropenoic acid (cinnamic acid)
Procedure
FUME HOOD
Problems
Further reading
Experiment 44 Condensation of benzaldehyde with acetone: the Claisen–Schmidt reaction
Procedure
FUME HOOD
1 Preparation of ( E )‐4‐phenylbut‐3‐en‐2‐one (benzylideneacetone)
2 Preparation of 1,5‐diphenyl‐( E,E )‐1,4‐pentadien‐3‐one (dibenzylideneacetone)
Problems
Further reading
Experiment 45 Synthesis of 5,5‐dimethylcyclohexane‐1,3‐dione (dimedone)
Procedure
FUME HOOD
Problems
Experiment 46 Reactions of indole: the Mannich and Vilsmeier reactions
Procedure
FUME HOOD
1 Preparation of gramine
2 Preparation of indole‐3‐carboxaldehyde
FUME HOOD
Problems
Further reading
Experiment 47 Preparation of 3‐methylcyclohex‐2‐enone
Procedure
FUME HOOD
Problems
Further reading
Experiment 48 Enamines: acetylation of cyclohexanone via its pyrrolidine enamine
Procedure
1 Preparation of 2‐acetylcyclohexanone
2 Preparation of 7‐oxooctanoic acid (optional)
Problems
Experiment 49 Enol derivatives: preparation of the enol acetate, trimethylsilyl enol ether and pyrrolidine enamine of 2‐methylcyclohexanone
Procedure
1 Preparation of the enol acetate of 2‐methylcyclohexanone
2 Preparation of the trimethylsilyl enol ether of 2‐methylcyclohexanone
3 Preparation of the pyrrolidine enamine of 2‐methylcyclohexanone
Problems
Further reading
Experiment 50 Preparation of (R)‐warfarin
Procedure
Problems
Further reading
Experiment 51 Reductive alkylation of enones: 2‐(prop‐2‐enyl)‐3‐methylcyclohexanone
Experiment 51 Reductive alkylation of enones: 2‐(prop‐2‐enyl)‐3‐methylcyclohexanone
Procedure
Problems
Further reading
Experiment 52 Lithium diisopropylamide as base: regioselectivity and stereoselectivity in enolate formation
Procedure
1 Formation of lithium diisopropylamide
2 Deprotonation and chlorotrimethylsilane quench
Problems
Further reading
Experiment 53 Dianions: aldol condensation of the dianion from ethyl 3‐oxobutanoate (ethyl acetoacetate) with benzophenone
Experiment 53 Dianions: aldol condensation of the dianion from ethyl 3‐oxobutanoate (ethyl acetoacetate) with benzophenone
Procedure
Problems
Further reading
8.3 Heteroatom‐stabilized carbanions
8.3.1 The Wittig reaction
Further reading
Experiment 54 Preparation of ( E )‐diphenylethene (stilbene) with ylid generation under phase transfer conditions
Procedure
Problems
Further reading
Experiment 55 Preparation of 4‐vinylbenzoic acid by a Wittig reaction in aqueous medium
Procedure
Preparation of 4‐carboxybenzyltriphenylphosphonium bromide
Preparation of 4‐vinylbenzoic acid
Problems
Experiment 56 A Wittig reaction involving preparation and isolation of a stabilized ylid: conversion of 1‐bromobutyrolactone to α‐methylenebutyrolactone
Procedure
1 Preparation of 1‐butyrolactonyltriphenylphosphonium bromide
2 Preparation and isolation of 1‐butyrolactonylidene triphenylphosphorane
3 Preparation of α‐methylenebutyrolactone
Problems
Further reading
8.3.2 The Horner–Wadsworth–Emmons reaction
Experiment 57 Preparation of ( E,E )‐1,4‐diphenyl‐1,3‐butadiene
Procedure
1 Preparation of diethyl benzylphosphonate
Preparation of (E,E)‐1,4‐diphenyl‐1,3‐butadiene
Problems
Further reading
8.3.3 Sulfur ylids
Experiment 58 Sulfur ylids: preparation of methylenecyclohexane oxide (1‐oxaspiro[2.5]octane)
Experiment 58 Sulfur ylids: preparation of methylenecyclohexane oxide (1‐oxaspiro[2.5]octane)
Procedure
1 Preparation of dimethylsulfoxonium methylide
2 Preparation of methylenecyclohexane oxide
Problems
Further reading
8.3.4 Umpolung of reactivity
Experiment 59 Illustration of ‘umpolung’ in organic synthesis: synthesis of ethyl phenylpyruvate via alkylation of ethyl 1,3‐dithiane‐2‐carboxylate, followed by oxidative hydrolysis with N‐bromosuccinimide
Procedure
1 Preparation of ethyl 2‐benzyl‐1,3‐dithiane‐2‐carboxylate
2 Preparation of ethyl phenylpyruvate
Problems
Further reading
8.4 Aromatic electrophilic substitution
Experiment 60 Nitration of methyl benzoate
Procedure
Problems
8.4.1 The Friedel–Crafts reaction
Experiment 61 4‐Bromobenzophenone by the Friedel–Crafts reaction
Procedure
Problem
Experiment 62 Friedel–Crafts acetylation of ferrocene using different Lewis acid catalysts and identification of the products by 1H NMR spectroscopy
Procedure
1 Boron trifluoride‐catalysed acetylation of ferrocene
2 Aluminium chloride‐catalysed acetylation of ferrocene
Problems
Further reading
Experiment 63 Fries rearrangement of phenyl acetate: preparation of 2‐hydroxyacetophenone
Experiment 63 Fries rearrangement of phenyl acetate: preparation of 2‐hydroxyacetophenone
Procedure
1 Preparation of 2‐hydroxyacetophenone
2 Isolation of the 4‐hydroxyacetophenone (optional)
Problems
8.5 Pericyclic reactions
Experiment 64 Diels–Alder preparation of cis‐cyclohex‐4‐ene‐1,2‐dicarboxylic acid
Experiment 64 Diels–Alder preparation of cis‐cyclohex‐4‐ene‐1,2‐dicarboxylic acid
Procedure
1 Preparation of cis‐cyclohex‐4‐ene‐1,2‐dicarboxylic anhydride
2 Hydrolysis of initial anhydride adduct to cis‐cyclohex‐4‐ene‐1,2‐dicarboxylic acid
Problems
Experiment 65 Formation of a Diels–Alder adduct
Procedure
Problems
Experiment 66 Preparation of 2,3‐dimethyl‐1,3‐butadiene and its Diels–Alder reaction with butenedioic anhydride (maleic anhydride)
Procedure
1 Preparation of 2,3‐dimethyl‐1,3‐butadiene
2 Diels–Alder reaction
Problems
Experiment 67 Benzyne: Diels–Alder reaction with furan
Procedure
1 Preparation of 1,4‐dihydronaphthalene‐1,4‐endoxide
2 Treatment of 1,4‐dihydronaphthalene‐1,4‐endoxide with acid (optional)
Problems
Further reading
Experiment 68 [2 + 2]‐ Cycloaddition of cyclopentadiene to dichloroketene: 7,7‐dichlorobicyclo[3.2.0]hept‐2‐en‐6‐one
Procedure
1 Preparation of cyclopentadiene from dicyclopentadiene
2 Preparation of 7,7‐dichlorobicyclo[3.2.0]hept‐2‐en‐6‐one
3 Preparation of bicyclo[3.2.0]hept‐2‐en‐6‐one (optional)
Problems
Further reading
Experiment 69 Generation of dichlorocarbene and addition to styrene: preparation of (2,2‐dichlorocyclopropyl)benzene
Procedure
Problems
Further reading
Experiment 70 Claisen rearrangement of 2‐propenyloxybenzene (allyl phenyl ether): preparation and reactions of 2‐allylphenol
Procedure
1 Preparation of allyl phenyl ether
2 Preparation of 2‐allylphenol
3 Treatment of 2‐allylphenol with KOH (optional)
4 Treatment of 2‐allylphenol with HBr (optional)
Problems
Further reading
Experiment 71 Preparation of 3,5‐diphenylisoxazoline by a 1,3‐dipolar cycloaddition
Procedure
Problems
Further reading
8.6 Metal‐mediated coupling reactions
Experiment 72 Preparation of 2‐methyl‐4‐(4‐nitrophenyl)but‐3‐yn‐2‐ol
Experiment 72 Preparation of 2‐methyl‐4‐(4‐nitrophenyl)but‐3‐yn‐2‐ol
Procedure
Problems
Further reading
Experiment 73 Preparation and use of a palladium catalyst suitable for application in a Suzuki– Miyaura cross‐coupling reaction
Procedure
1 Preparation of palladium catalyst
2 Preparation of biphenyl‐4‐carboxylic acid
Problems
Further reading
Experiment 74 Preparation of unsymmetrical biaryls by Suzuki–Miyaura cross‐coupling
Procedure
Problems
Further reading
Experiment 75 Preparation of diethyl cyclopent‐3‐ene‐1,1‐dicarboxylate
Procedure
Problem
Further reading
9 Experiments using enabling technologies
9.1 Microwave chemistry
Further reading
Experiment 76 Preparation of 2‐amino‐4‐phenylthiazole
Procedure
Problems
Experiment 77 Preparation of 5,6‐dimethyl‐3a,4,7,7a‐tetrahydroisobenzofuran‐1,3‐dione
Experiment 77 Preparation of 5,6‐dimethyl‐3a,4,7,7a‐tetrahydroisobenzofuran‐1,3‐dione
Procedure
Problems
Experiment 78 The Fischer indole synthesis: preparation of 1,2,3,4‐tetrahydrocarbazole
Experiment 78 The Fischer indole synthesis: preparation of 1,2,3,4‐tetrahydrocarbazole
Procedure
Problems
Further reading
Experiment 79 Preparation of trans‐ethyl cinnamate [(E)‐ethyl 3‐phenylpropenoate]
Experiment 79 Preparation of trans‐ethyl cinnamate [(E)‐ethyl 3‐phenylpropenoate]
Procedure
Problems
Further reading
9.2 Flow chemistry
9.2.1 Equipment
9.2.2 Performing a reaction in flow
Further reading
Experiment 80 An introductory experiment using flow chemistry
Procedure
1 Prepare the reagent reservoirs
2 Set up the flow unit
3 Performing the experiment
Experiment 81 Preparation of propyl benzoate using flow chemistry
Procedure
1 Prepare the reagent reservoirs
2 Set up the flow unit
3 Preparation of propyl benzoate
4 Product purification
Problems
Experiment 82 Preparation of diethyl cyclopent‐3‐ene‐1,1‐dicarboxylate using flow chemistry
Procedure
1 Prepare the reagent reservoirs
2 Set up the flow unit
3 Preparation of diethyl cyclopent‐3‐ene‐1,1‐dicarboxylate
4 Product purification
Problems
Experiment 83 Preparation of biphenyl using flow chemistry
Procedure
1 Prepare the reagent reservoirs
2 Set up the flow unit
3 Preparation of biphenyl
4 Product purification
Problems
10 Projects
10.1 Natural product isolation and identification
Experiment 84 Isolation of eugenol, the fragrant component of cloves, and lycopene, a colouring component of tomatoes
Procedure
1 Isolation of eugenol
2 Isolation of lycopene
Problems
Experiment 85 Isolation and characterization of limonene, the major component of the essential oil of citrus fruit
Procedure
Problems
Further reading
Experiment 86 Isolation of caffeine from tea and theobromine from cocoa
Procedure
1 Isolation of caffeine
2 Isolation of theobromine
Problems
Further reading
10.2 Project in organic synthesis
Experiment 87 Preparation of and use of  Jacobsen’s catalyst
Procedure
1 Preparation and recrystallization of (R,R)‐(+)‐1,2‐diaminocyclohexane L‐tartrate
2 Preparation of (R,R)‐N,N′‐bis(3,5‐di‐t‐butylsalicylidene)‐1,2‐cyclohexanediamine
2 Preparation of (R,R)‐N,N′‐bis(3,5‐di‐t‐butylsalicylidene)‐1,2‐cyclohexanediamine
3 Preparation of [(R,R)‐N,N′‐bis(3,5‐di‐t‐butylsalicylidene)‐1,2‐cyclohexanediaminato(2–)]manganese(III) chloride (Jacobsen’s catalyst)
3 Preparation of [(R,R)‐N,N′‐bis(3,5‐di‐t‐butylsalicylidene)‐1,2‐cyclohexanediaminato(2–)]manganese(III) chloride (Jacobsen’s catalyst)
4 Preparation of 1,2‐dihydronaphthalene oxide
Problems
Further reading
Experiment 88 Dyes: preparation and use of indigo
Procedure
1 Preparation of indigo
2 Vat dying of cotton
Problems
Further reading
Experiment 89 Synthesis of flavone
Procedure
1 Preparation of 2‐benzoyloxyacetophenone
2 Preparation of 2‐hydroxydibenzoylmethane
3 Preparation of flavone
Problems
Further reading
10.2.1 Syntheses of pheromones
Experiment 90 Insect pheromones: synthesis of (±)‐4‐methylheptan‐3‐ol and (±)‐4‐methylheptan‐3‐one
Procedure
1 Preparation of 4‐methylheptan‐3‐ol
2 Preparation of 4‐methylheptan‐3‐one
Problems
Further reading
Experiment 91 Insect pheromones: methyl 9‐oxodec‐2‐enoate, the queen bee pheromone
Procedure
1 Preparation of 1‐methylcycloheptanol
2 Preparation of 1‐methylcycloheptene
3 Preparation of 7‐oxooctanal
4 Preparation of methyl 9‐oxodec‐2‐enoate (queen bee pheromone methyl ester)
5 Preparation of methyl (triphenylphosphoranylidene)acetate (optional)
Problems
Further reading
Experiment 92 Synthesis of 6‐nitrosaccharin
Procedure
1 Preparation f 4‐nitrotoluene‐2‐sulfonamide
2 Preparation of 6‐nitrosaccharin
Problems
Further reading
10.2.2 Macrocyclic compounds
Experiment 93 Preparation of copper phthalocyanine
Procedure
Problems
Further reading
Experiment 94 Synthesis of tetraphenylporphin and its copper complex
Procedure
1 Preparation of meso‐tetraphenylporphin
2 Preparation of TPP copper complex [5,10,15,20‐tetraphenyl porphyrinatocopper(II)]
Problems
Further reading
10.2.3 Chemiluminescence
Experiment 95 Observation of sensitized fluorescence in an alumina‐supported oxalate system
Experiment 95 Observation of sensitized fluorescence in an alumina‐supported oxalate system
Procedure
Further reading
10.2.4 Photochromism and piezochromism
Experiment 96 Synthesis of 2‐[(2,4‐dinitrophenyl)‐methyl]pyridine, a reversibly photochromic compound
Procedure
Problems
Further reading
Experiment 97 Preparation of 2,4,5‐triphenylimidazole (lophine) and conversion into its piezochromic and photochromic dimers
Procedure
1 Preparation of 2,4,5‐triphenylimidazole
2 Preparation of piezochromic and photochromic dimers
Problems
Further reading
10.3 Aspects of physical organic chemistry
Experiment 98 Preparation and properties of the stabilized carbocations triphenylmethyl fluoroborate and tropylium fluoroborate
Procedure
1 Preparation of triphenylmethyl fluoroborate
2 Preparation of tropylium fluoroborate
Problems
Experiment 99 Measurement of acid dissociation constants of phenols: demonstration of a linear free‐energy relationship
Procedure
Calculation
Linear free‐energy relationship
Problems
Experiment 100 Measurement of solvent polarity
Procedure
Problems
Further reading
Experiment 101 Preparation of 1‐deuterio‐1‐phenylethanol and measurement of a kinetic isotope effect in the oxidation to acetophenone
Procedure
1 Preparation of 1‐deuterio‐1‐phenylethanol
2 Measurement of kinetic isotope effect
Problem
Further reading
Experiment 102 Tautomeric systems
Procedure
Problems
Experiment 103 Kinetic versus thermodynamic control of reaction pathways: study of the competitive semicarbazone formation from cyclohexanone and 2‐furaldehyde (furfural)
Procedure
1 Preparation of the pure semicarbazones of cyclohexanone and 2‐furaldehyde and observation of precipitation times
2 Competitive semicarbazone formation from cyclohexanone and 2‐furaldehyde under thermodynamic control
3 Competitive semicarbazone formation from cyclohexanone and 2‐ furaldehyde under kinetic control
4 Determination of the composition of the kinetic and thermodynamic product mixtures by UV spectroscopy (optional)
Problem
Experiment 104 Determination of an equilibrium constant by 1H NMR spectroscopy
Procedure
1 Preparation of acetophenone azine
2 Preparation of benzaldehyde azine
3 Preparation of mixed acetophenone benzaldehyde azine
4 Equilibration studies and determination of KE  by NMR spectroscopy
Problems
Further reading
Appendices
Appendix 1 Organic solvents
Reference
IR correlation tables
NMR correlation tables
UV correlation tables
MS correlation tables
The PeriodicTable
IR correlation tables
NMR correlation tables
UV correlation tables
MS correlation tables
The Periodic Table
Index of chemicals
General Index
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