TABLE OF CONTENTS

1. Chapter One - Introduction

• 1.1 Introduction to cancer
• 1.1.1 Types of tumours
• 1.1.2 Progression and metastasis
• 1.1.3 Treatment
• 1.2 Chemical carcinogens
• 1.2.1 Historical background
• 1.2.2 Chemical properties of carcinogens
• 1.2.3 Metabolic and chemical activation of carcinogens
• 1.2.4 Aromatic amines
• 1.3 Nitrenium ions
• 1.3.1 Electronic structure
• 1.3.2 Alkylnitrenium ions
• 1.3.3 Arylnitrenium ions
• 1.3.4 Heteroatom stabilisation of nitrenium ions
• 1.4 Goals

2. Chapter One - Acid-catalysed solvolysis of alkyl N-acyloxybenzohydroxamates

• 2.1 General synthesis of alkyl N-acyloxybenzohydroxamates
• 2.2 Acid-catalysed solvolysis of butyl Nacetoxybenzohydroxamates
• 2.2.1 Background
• 2.2.2 Preliminary kinetics - NMR monitoring of reaction dynamics
• 2.2.3 AAl1 solvolysis of alkyl N-acetoxybenzohydroxamate
• 2.2.4 Arrhenius results for butyl Nacetoxybenzohydroxamate
• 2.2.5 Synthesis and reactivity of butyl N-acetoxy-(parasubstituted) benzohydroxamates
• 2.2.6 Hammett correlation
• 2.2.7 Analysis of solvolysis products
• 2.2.8 Solvolysis mechanisms
• 2.2.9 Butanal and benzohydroxamic acid
• 2.2.10 Butanol and nitrosocarbonylbenzene
• 2.2.11 Butyl benzoate
• 2.3 Acid-catalysed solvolysis of benzyl Nacetoxybenzohydroxamate
• 2.3.1 Background
• 2.3.2 Synthesis of benzyl Nacetoxybenzohydroxamates
• 2.3.3 Acetoxylation of benzyl Nacetoxybenzohydroxamates
• 2.3.4 Acid-catalysed solvolysis of benzyl Nacetoxybenzohydroxamates
• 2.3.5 Enthalpy vs entropy relationship
• 2.3.6 Analysis of solvolysis products
• 2.3.7 Benzaldehyde and benzohydroxamic acid
• 2.3.8 Benzoic acid, benzyl alcohol and benzoic anhydride
• 2.4 Acid-catalysed solvolysis of benzyl Nbenzoyloxybenzohydroxamates
• 2.4.1 Background
• 2.4.2 Synthesis of benzyl Nbenzoyloxybenzohydroxamates
• 2.4.3 Kinetic results
• 2.4.4 Hammett correlation
• 2.5 Acid-catalysed solvolysis summary

3. Chapter Three - Reactions of alkyl Nacetoxybenzohydroxamates with base

• 3.1 Base hydrolysis of butyl Nacetoxybenzohydroxamate
• 3.1.1 Products under basic conditions
• 3.2 Base hydrolysis of benzyl Nbenzoyloxybenzohydroxamates
• 3.3 Base hydrolysis summary

4. Chapter Four - Mutagenicity of alkyl Nacetoxybenzohydroxamates

• 4.1 The Ames test and factors controlling mutagenicity
• 4.1.1 Transportation across the cell
• 4.1.2 Assay procedure
• 4.2 Mutagenicity of butyl Nacetoxybenzohydroxamates
• 4.2.1 Butyl Nacetoxybenzohydroxamate
• 4.3 Mutagenicity of benzyl Nacetoxybenzohydroxamates
• 4.4 Mutagenicity of benzyl Nbenzoyloxybenzohydroxamates
• 4.5 Summary of mutagenicity effects
• 4.5.1 Hydrophobic effects
• 4.5.2 Nitro-aromatics
• 4.5.3 Summary of mutagenicity data

5. Chapter Five - Conclusion

• 5.1 Conclusion

6. Chapter Six - Experimental

• 6.1 General
• 6.2 Handling of suspect mutagenic compounds
• 6.3 Syntheses
• 6.3.1 General synthesis of alkyl parasubstituted benzohydroxamates
• 6.3.2 General synthesis of parasubstituted benzyl benzohydroxamates
• 6.3.3 General synthesis of parasubstituted benzyl alcohols
• 6.3.4 General synthesis of parasubstituted benzyl bromides
• 6.3.5 General synthesis of parasubstituted benzylbenzohydroxamates
• 6.3.6 N-Chlorination of alkyl benzohydroxamates
• 6.3.7 General synthesis of alkyl N-acetoxy benzohydroxamates
• 6.3.8 Butyl Nacetoxybenzohydroxamates
• 6.3.9 Benzyl Nacetoxybenzohydroxamates
• 6.3.10 Benzyl Nbenzoyloxybenzohydroxamates
• 6.4 Miscellaneous syntheses
• 6.5 Acid-catalysed solvolysis procedure
• 6.6 Base hydrolysis procedure
• 6.7 Ester crossover experiments
• 6.7.1 Synthesis and decomposition studies of N-4-chlorobenzoyl-N-butoxy-N'benzoyl-N'benzyloxyhydrazine
• 6.8 Nitrene trapping Experiments

7. Appendix

• 7.1 Acid-catalysed solvolysis data

8. Bibliography