CARBON MONOXIDE AS REAGENT IN THE FORMYLATION OF AROMATIC COMPOUNDS by Johannes Alexander Willemse Dissertation in fulfillment of the requirements for the degree Magister Scientiae in Chemistry in the Faculty of Science at the Rand Afrikaans University Supervisor: Prof. C.W. Holzapfel Co-supervisor: Dr B.C.B. Bezuidenhoudt September 2003 Acknowledgements My sincere gratitude is extended to the following people: • Prof. C.W. Holzapfel for his tremendous enthusiasm and support • Dr. B.C.B Bezuidenhoudt for his proficient tutelage and forbearance during this study • Sasol for financial support • Ms A. Ranwell and M. Ajam for supplying most of the ionic liquids • Dr. J. Coetzee and Ms M. Kirk for NMR data recording and interpretation • Mr. A. Tolmay for Mass Spectrometry data recording • My colleagues drr. P. van Heerden, J. Dixon and C. Grove for their support • This study is dedicated to my wife Marietjie; my daughter Luchelle and son Wynand and with special recognition to my parents for their sacrifices and devotion Phillipians 4:13: “I can do all things through Christ, who strengthens me” TABLE OF CONTENTS ABBREVIATIONS ......................................................................................................................................I SYNOPSIS.................................................................................................................................................II OPSOMMING .......................................................................................................................................... IV CHAPTER 1...............................................................................................................................................1 AROMATIC ALDEHYDE SYNTHESES ....................................................................................................1 1. INTRODUCTION ...............................................................................................................................1 1.1 Comparison of Ketone and Aldehyde Syntheses........................................................................1 2. FORMYLATING AGENTS .................................................................................................................2 2.1 Formic acid and Derivatives ........................................................................................................2 2.2 Gattermann-Koch Reaction.........................................................................................................7 2.3 Chloromethylene Dibenzoate and Dichloro Alkyl Ethers ..........................................................12 2.4 Gattermann Synthesis...............................................................................................................13 2.5 Formyl Chloride Oxime and Ethoxalyl Chloride ........................................................................14 2.6 Vilsmeier-Haack reaction ..........................................................................................................16 2.7 Formylation of Organometallic Compounds..............................................................................18 2.8 Selective ortho formylation of phenols ......................................................................................20 2.9 Duff Reaction.............................................................................................................................22 2.10 Glyoxylic Acid ..........................................................................................................................23 2.11 Saligenin Reaction ..................................................................................................................23 2.12 Reimer Tiemann Reaction.......................................................................................................24 2.13 Alternative Reactions ..............................................................................................................26 CHAPTER 2.............................................................................................................................................34 CO CARBONYLATION OF AROMATIC COMPOUNDS........................................................................34 1. INTRODUCTION .............................................................................................................................34 2. FORMYLATION UTILIZING HF/BF3 AS CATALYST .......................................................................36 2.1 The Carbon Monoxide Molecule ...............................................................................................36 2.2 Properties of hydrogen fluoride .................................................................................................37 2.3 Properties of boron trifluoride....................................................................................................38 2.4 Properties of the active HF/BF3 catalyst....................................................................................39 3. SUBSTRATE AND CATALYST EVALUATION................................................................................42 3.1 Phenol and Anisole ...................................................................................................................42 3.2 Evaluation of Other Catalyst/Reaction Systems .......................................................................45 3.3 Mechanism Studies ...................................................................................................................50 3.3.1 Formylation Mechanisms ..................................................................................................................50 3.3.2 Deuterium Labelling Experiments .....................................................................................................53 3.3.3 Mechanism of Secondary Product Formation ...................................................................................53 3.4 Formylation of other substrates.................................................................................................53 3.5 Conclusion.................................................................................................................................53 4. IONIC LIQUIDS AS SOLVENT FOR HF/BF3 CATALYSED REACTIONS .......................................53 4.1 Introduction................................................................................................................................53 4.2 General definitions and characteristics of ionic liquids .............................................................53 4.3 Synthesis of ionic liquids ...........................................................................................................53 4.4 Acidity and coordination ability of ionic liquids ..........................................................................53 4.5 Ionic Liquids as Solvents for Transition Metal Catalyzed Reactions.........................................53 4.6 Formylation Reactions in Ionic Liquids......................................................................................53 4.7 Conclusions...............................................................................................................................53 CHAPTER 3.............................................................................................................................................53 EXPERIMENTAL .....................................................................................................................................53 1 INTRODUCTION ..............................................................................................................................53 1.1 Personal Protective Equipment.................................................................................................53 1.2 Reactor ......................................................................................................................................53 1.3 Reagents ...................................................................................................................................53 2 GENERAL EXPERIMENTAL PROCEDURE ....................................................................................53 2.1 HF Formylation Reactions.........................................................................................................53 2.2 HF Formylation Reactions in Ionic Liquid..................................................................................53 2.3 Deuterium Fluoride Preparation and DF Formylation Reactions ..............................................53 2.4 Preparation of di-(4-methoxyphenyl)methanol..........................................................................53 2.5 Ionic Liquid Preparation.............................................................................................................53 2.6 Chromatography........................................................................................................................53 2.7 Drying of Reagents....................................................................................................................53 2.8 Spectrometric and Spectroscopic Methods...............................................................................53 ADDENDUM: NMR-, MS- AND GC SPECTRA OF KEY COMPOUNDS...............................................53 Abbreviations NMR nuclear magnetic resonance MO molecular orbital M.p. melting point B.p. boiling point FID flame