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Chiral Chromatography 1998 - Scott & Beesley

Sep 12, 2014



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Chiral Chromatography

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SEPARATION SCIENCE SERIES Editors: Raymond P.W. Scott, Colin Simpson and Elena D. Katz Quantitative Analysis using Chromatographic Techniques Edited by Elena D. Katz The Analysis of Drugs of Abuse Edited by Terry A. Gough Liquid Chromatography Column Theory Edited by Raymond P.W. Scott Silica Gel and Bonded Phases: Their Production, Properties and Use in LC Edited by Raymond P.W. Scott Capillary Gas Chromatography Principles and Methods in Biotechnology by David W. Grant High Performance Liquid Chromatography: Principles and Methods in Biotechnology Edited by Elena D. Kratz Tandem Techniques by Raymond P.W. Scott Chiral Chromatography by Thomas E. Beesley and Raymond P.W. Scott

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Chiral Chromatographyby Thomas E. Beesley Advanced Separation Technology Inc., New York, USA and Raymond P.W. Scott Georgetown University, Washington DC, USA and Birkbeck College, University of London, UK

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Copyright 1998 by John Wiley & Sons Ltd. Baffins Lane, Chichester West Sussex PO19 1UD, England National Chichester (01243) 779777 International (+44) 1243 779777 e-mail (for orders and customer service enquiries): [email protected] Visit our Home Page on or All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, scanning or otherwise, except under the terms of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London, W1P 9HE, UK, without the permission in writing of the publisher. Other Wiley Editorial Offices John Wiley & Sons, Inc., 605 Third Avenue, New York, NY 10158-0012, USA Wiley-VCH Verlag GmbH, Pappelallee 3, D-69469 Weinheim, Germany Jacaranda Wiley Ltd, 33 Park Road, Milton, Queensland 4064, Australia John Wiley & Sons (Asia) Pte Ltd, 2 Clementi Loop #02-01, Jin Xing Distripark, Singapore 129809 John Wiley & Sons (Canada) Ltd, 22 Worcester Road, Rexdale, Ontario M9W 1L1, Canada British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0 471 97427 7 Produced from camera ready copy supplied by the authors Printed and bound in Great Britain by Bookcraft (Bath) Ltd This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production.

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PrefaceIn the world of science, nothing invigorates the mind so much as to watch a concept develop from some small seed of discovery to a universally applicable technology. In the last four decades, chromatography, the once mysterious and very crude technique, has grown into a very sophisticated and reliable separation methodology. Over the last decade, the application of the accumulated knowledge to the once esoteric field of chiral separations has made impressive advances particularly in the last three years. The chromatography of enantiomers has required the preparation of highly structured phases, which had to be designed to have a direct bearing on the nature and the chemistry of the materials to be separated. New terms had to be introduced and defined, such as three point interaction and inclusion complexation to describe some of the new interactive mechanisms that were invoked. As will be apparent from this book, however, the basic chromatography terms and the physical chemical principles that determine that a chromatographic separation is possible remain the same. In dealing comprehensively with the subject of chiral chromatography, a significant amount of theory must be included, but we have tried to present this in a manner that explains the interactions that takes place and provides a rational direction that can be taken to solve practical problems. Having been involved in chromatography for many years (our combined experience extending over three quarters of a century) we find it gratifying to see the very substantial increases in successful chiral separations that are currently published in the field. Starting from the pioneering work of Gil-Av (1966) and Bayer (1974) followed by that of Okamato and Pirkle and culminating with the recent, highly innovative phases, introduced by Armstrong, chiral chromatography has now reached a high degree of sophistication. The creation of the cyclodextrin phases and the introduction of the macrolytic antibiotics by Armstrong has brought new incentives to the field and many new areas of application. This book has been written to serve both the novice in the field and the experienced chromatographer. In addition to giving detailed information on chiral separations, it also discusses the principles involved in chiral selectivity and, for those new to the technique, describes the fundamentals of a chromatographic separation and the essential apparatus needed to carry it out. To make the book as complete as possible we have included chapters on preparative chiral chromatography and some basic

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information on chiral capillary electrophoresis and electro-chromatography. Finally, to help readers choose the correct phase system and operating conditions for their particular sample, we have incorporated experimental selection schemes for the four major chiral stationary phases that are commercially available. THOMAS. E. BEESLEY RAYMOND P. W. SCOTT NOVEMBER 1998

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AcknowledgmentsIn the preparation of any technical book, information must be gathered from a variety of sources. The authors would like to take this opportunity to thank the many journals who have granted us permission to reproduce diagrams from their publications, and those chromatography vendors who have supplied us with the technical details of their products. In particular, we would like to thank the companies Advanced Separations Technologies Inc. (ASTEC), Chromtech AB, Regis Technologies, Chiral Technologies, and Supelco for providing both technical data and permission to reproduce their product bibliographies. Special thanks are also due to Advanced Separations Technologies Inc. (ASTEC) who contributed laboratory facilities for data collection and to their staff members, Dr. Heng Liang Jin and Mr. B Buglio, who helped provide the chiral retention data that is used in the optimization procedures. Finally, thanks are due to the production department of John Wiley and Sons for their careful review of the manuscript before publication. In particular we appreciate the efforts of Mr. Martin Tribe and his assistants for their much appreciated comments and advice. THOMAS E. BEESLEY RAYMOND P. W. SCOTT OCTOBER 1998

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ContentsChapter 1 An Introduction to Chiral Chromatography An Historical Perspective A Short Introduction to Stereochemistry Polarization Modulation Practical Chiral Measuring Devices Configuration Specifications Diastereoisomers Anomers Epimers Meso Structures Separation Techniques for Chiral Chemistry Synopsis References Chapter 2 Mechanism of Solute Retention The Plate Theory The Retention Volume of a Solute The Capacity Ratio of a Solute The Separation Ratio 1

1 3 7 8 15 18 20 20 22 23 25 27 29

30 34 37 38

The Thermodynamic Properties of the Distribution Coefficient The Availability of the Stationary Phase Synopsis References Chapter 3 Molecular Interactions Dispersion Forces Polar Forces Dipole-Dipole Interactions Dipole-Induced-Dipole Interactions

39 47 50 51 53

54 56 57 59

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Ionic Forces Hydrophobic and Hydrophilic Interactions Molecular Interactions in Mixed Phases Chiral Additives Synopsis References Chapter 4 The Basic Gas Chromatograph Gas Supplies Sampling Devices Injection Systems for Packed Columns Injection Systems for Small Diameter Capillary Columns Injection Systems for Large Bore Capillary Columns Automatic Injection Systems The Column Oven and Temperature Programmer Detectors Detector Specifications Detector Response Detector Sensitivity or Minimum Detectable Concentration Pressure Sensitivity Flow Sensitivity Temperature Sensitivity

60 61 65 72 76 77 79

81 83 83 85 86 88 88 89 90 93 93 94 95 95

The Flame Ionization Detector The Nitrogen Phosphorous Detector (NPD) The Electron Capture Detector The Katharometer (Thermal Conductivity and Hot Wire) Detector Data Acquisition and Processing Synopsis References Chapter 5 GC Chiral Stationary Phases and Columns Early Days in Chiral GC Chiral Stationary Phases for Gas Chromatography Small Molecule Stationary Phases Chiral Polysiloxane Stationary Phases Chiral Metal Chelating Stationary Phases Cyclodextrin Chiral Stationary Phases

95 97 98 101 103 104 106 107

108 112 112 114 116 119

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Factors Controlling Selectivity Open Tubular Columns Dynamic Coating Static Coating Column Regeneration Capillary Column Design and Choice Stationary Phases for the GC Separation of Chiral Substances Synopsis References Chapter 6 Chiral Gas Chromatography Applications The Basic Principles of Chiral Selectivity Test Mixtures Elution Reversal of Enantiomers Selectivity Characteristics of the Different Cyclodextrins The Effect of Solute Derivatization on Chiral Selectivity Chiral Separations of Essential Oils Pharmaceutical Applications of Chiral Gas Chromatography General Applications of Chiral Chromatography Synopsis References Chapter 7

123 124 125 127 127 129 136 138 140 141

141 143 146 149 154 156 165 169 171 172 173

The Basic Liquid Chromatograph The Basic LC Layout Mobile Phase Reservoirs The Solvent Programmer The High-Pressure Mixing Solvent Programmer The Low-Pressure Mixing Solvent Programmer The Mobile Phase Pump The Sample Valve The Column and