Solvents and solvent effects in organic chemistry fourth updated and expanded edition

Thomas WeltonSolvents and Solvent E¤ects inOrganic ChemistrySolvents and Solvent Effects in Organic Chemistry, Fourth Edition.. Maria Reichardt, Marburg, Solvents and Solvent Effects in

Thomas WeltonSolvents and Solvent E¤ects inOrganic Chemistry

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

Leitner, W., Jessop, P G., Li, C.-J.,

Wasserscheid, P., Stark, A (Eds.)

Handbook of Green Chemistry –

Solvent-free Organic Synthesis

468 pages with approx 261 figures

2009

Hardcover

ISBN: 978-3-527-32264-0

Carrea, G., Riva, S (Eds.)

Organic Synthesis with Enzymes

Bogdal, D., Prociak, A

Microwave-Enhanced Polymer Chemistry and Technology

280 pages 2007 Hardcover ISBN: 978-0-8138-2537-3

Lindstro¨m, U M (Ed.)Organic Reactions in WaterPrinciples, Strategies and Applications

424 pages Hardcover ISBN: 978-1-4051-3890-1

Solvents and Solvent E¤ects in Organic Chemistry

Fourth, Updated and Enlarged Edition

Prof Dr Christian Reichardt

Imperial College London

South Kensington Campus

Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.: applied for British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche Nationalbibliothek

The Deutsche Nationalbibliothek lists this cation in the Deutsche Nationalbibliografie; de- tailed bibliographic data are available on the In- ternet at http://dnb.d-nb.de.

publi-6 2011 Wiley-VCH Verlag & Co KGaA, Boschstrasse 12, 69469 Weinheim, Germany All rights reserved (including those of translation into other languages) No part of this book may

be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted

or translated into a machine language without written permission from the publishers.

Registered names, trademarks, etc used in this book, even when not specifically marked as such, are not to be considered unprotected by law Cover Grafik-Design Schulz, Fußgo¨nheim Typesetting Asco Typesetters, Hong Kong Printing and Binding Strauss GmbH, Mo¨rlenbach

Printed in the Federal Republic of Germany Printed on acid-free paper

ISBN 978-3-527-32473-6

and in memory of my parents

C R.

To Mike

and my parents

T W.

About 40 years ago, in 1969, a German paperback entitled Lo¨sungsmittele¤ekte in derorganischen Chemie, written by the first author, was published by Verlag Chemie inWeinheim Based on this paperback and its second edition in 1973, an enlarged Englishedition called Solvent E¤ects in Organic Chemistry appeared in 1979, followed by asecond English edition in 1988 with the now enlarged title Solvents and Solvent E¤ects inOrganic Chemistry A first and second reprint in 2004 and 2005 of the third, updatedand enlarged English edition of this book, published in 2003, demonstrate the continu-ing common interest in the study of solvent e¤ects on chemical reactions and physicalprocesses This and the progress that has been made in recent years in this field of re-search encouraged us to present now to the interested reader a fourth, again updatedand enlarged, edition of this book This was only possible because a junior authorhelped the meanwhile retired senior author with the preparation of the manuscript forthis new edition, particularly in writing the new Chapter 8.

This new chapter deals with the relationship between solvents and green try, the classification of solvents by their environmental impact, and the replacement oftraditional by non-traditional solvents for chemical reactions

chemis-During the seven years after publication of the third edition in 2003, the number

of solvent-dependent processes studied has increased to such an extent (particularly inthe field of ionic liquids) that only a careful selection of instructive and representativeexamples could be additionally included in this fourth edition The literature has beencovered up to 2009, partly up to 2010 New references have been added at the end of thereference list of each chapter

recom-mended by the respective IUPAC Commissions has again been made in this fourthedition

For useful comments and valuable suggestions we thank many colleagues, inparticular Prof Dr N O Mchedlov-Petrossyan, Kharkov/Ukraine, Dr T Rager,Basel/Switzerland, and Prof Dr G N Papatheodorou, Rio/Greece For their assis-tance in providing us with di‰cult to obtain literature and in preparing the final manu-script, C R thanks Mrs B Becht-Schro¨der (librarian) and Mr G Scha¨fer (technician)

of the Department of Chemistry, Marburg, and also Mrs Maria Reichardt, Marburg,

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

a) G J Leigh, H A Favre, and W V Metanomski: Principles of Chemical Nomenclature –

A Guide to IUPAC Recommendations, Blackwell, Oxford, 1998; R Panico, W H Powell, and J.-C Richer: A Guide to IUPAC Nomenclature of Organic Compounds – Recommendations 1993, Blackwell, Oxford, 1993.

b) E R Cohen, T Cvitasˇ, J G Frey, B Holmstro¨m, K Kuchitsu, R Marquardt, I Mills,

F Pavese, M Quack, J Stohner, H L Strauss, M Takami, and A J Thor: Quantities, Units and Symbols in Physical Chemistry (IUPAC 2007), 3 rd ed., Royal Society of Chemistry, Cambridge, 2007.

c) P Mu¨ller: Glossary of Terms Used in Physical Organic Chemistry – IUPAC Recommendations

1994, Pure Appl Chem 66, 1077 (1994).

d) G H Aylward and T J V Findlay: SI Chemical Data, 6 th ed., Wiley, Milton/Australia, 2008; see also Bureau International des Poids et Mesures (BIPM): Le Syste`me International d’Unite´s (SI), 8 th ed., STEDI Media, Paris, 2006.

for her continuous support of this project T.W thanks the final-year Imperial CollegeChemistry students and Green Chemistry Master students for helpful discussions.

We both express our thanks to the sta¤ of Wiley-VCH Verlag GmbH, Weinheim,particularly to Dr Elke Maase and Dr Stefanie Volk, for their help and excellent work

in turning the manuscript into this final book

Summer 2010

Meeting the demand for the second edition of this book, which is – despite a reprint in

1990 – no longer available, and considering the progress that has been made during thelast decade in the study of solvent e¤ects in experimental and theoretical organic chem-istry, this improved third edition is presented to the interested reader

Following the same layout as in the second edition, all topics retained have beenbrought up to date, with smaller and larger changes and additions on nearly every page.Two Sections (4.4.7 and 5.5.13) are completely new, dealing with solvent e¤ects onhost/guest complexation equilibria and reactions in biphasic solvent systems and neo-teric solvents, respectively More than 900 new references have been added, giving pre-ference to review articles, and many older ones have been deleted New references eitherreplace older ones or are added to the end of the respective reference list of each chapter.The references cover the literature up to the end of 2001

From the vast number of published papers dealing with solvent e¤ects in all areas

of organic chemistry, only some illustrative examples from the didactic and systematicpoint of view could be selected This book is not a monograph covering all relevantliterature in this field of research The author, responsible for this subjective selec-tion, apologizes in advance to all chemists whose valuable work on solvent e¤ects isnot mentioned in this book However, using the reviews cited, the reader will find easyaccess to the full range of papers published in a certain field of research on solvente¤ects

Great progress has been made during the last decade in theoretical treatments ofsolvent e¤ects by various quantum-chemical methods and computational strategies.When indicated, relevant references are given to the respective solution reactions orabsorptions However, a critical evaluation of all the theoretical models and methodsused to calculate the di¤erential solvation of educts, activated complexes, products,ground and excited states, is outside the expertise of the present author Thus, a book onall kinds of theoretical calculations of solvent influences on chemical reactions andphysical absorptions has still to be written by someone else

recom-mended by the IUPAC commissions has also been made in this third edition

For comments and valuable suggestions I have to thank many colleagues, in ticular Prof E M Kosower, Tel Aviv/Israel, Prof R G Makitra, Lviv/Ukraine, Prof

par-N O Mchedlov-Petrossyan, Kharkiv/Ukraine, and Prof K Mo¨ckel, Mu¨hlhausen/Germany For their assistance in drawing formulae, preparing the indices, and provid-ing me with di‰cult to obtain literature, I thank Mr G Scha¨fer (technician), Mrs S.Schellenberg (secretary), and Mrs B Becht-Schro¨der (librarian), all at the Department

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

a) G J Leigh, H A Favre, and W V Metanomski: Principles of Chemical Nomenclature – A Guide to IUPAC Recommendations, Blackwell Science Publications, London, 1998.

b) I Mills, T Cvitasˇ, K Homann, N Kallay, and K Kuchitsu: Quantities, Units and Symbols in Physical Chemistry, 2 nd ed., Blackwell Science Publications, London, 1993.

c) P Mu¨ller: Glossary of Terms used in Physical Organic Chemistry – IUPAC Recommendations

1994, Pure Appl Chem 66, 1077 (1994).

d) G H Aylward and T J V Tristan: SI Chemical Data, 4 th ed., Wiley, Chichester, 1999; Datensammlung Chemie in SI-Einheiten, 3 rd ed., Wiley-VCH, Weinheim/Germany, 1999.

of Chemistry, Philipps University, Marburg/Germany Special thanks are due to thesta¤ of Wiley-VCH Verlag GmbH, Weinheim/Germany, particularly to Dr ElkeWestermann, for their fine work in turning the manuscript into the final book Lastly,

my biggest debt is to my wife Maria, not only for her assistance in the preparation of themanuscript, but also for her constant encouragement and support during the writing ofthis book

The response to the first English edition of this book, published in 1979, has been bothgratifying and encouraging Its mixed character, lying between that of a monograph and

a textbook, has obviously made it attractive to both the industrial and academic chemist

as well as the advanced student of chemistry

During the last eight years the study of solvent e¤ects on both chemical tions and absorption spectra has made much progress, and numerous interesting andfascinating examples have been described in the literature In particular, the study ofionic reactions in the gas phase – now possible due to new experimental techniques –has allowed direct comparisons between gas-phase and solution reactions This has led

reac-to a greater understanding of solution reactions Consequently, Chapters 4 and 5 havebeen enlarged to include a description of ionic gas-phase reactions compared to theirsolution counterparts

The number of well-studied solvent-dependent processes, i.e reactions andabsorptions in solution, has increased greatly since 1979 Only a representative selection

of the more instructive, recently studied examples could be included in this secondedition

The search for empirical parameters of solvent polarity and their applications

in multiparameter equations has recently been intensified, thus making it necessary torewrite large parts of Chapter 7

Special attention has been given to the chemical and physical properties oforganic solvents commonly used in daily laboratory work Therefore, all AppendixTables have been improved; some have been completely replaced by new ones A newwell-referenced table on solvent-drying has been added (Table A-3) Chapter 3 has beenenlarged, in particular by the inclusion of solvent classifications using multivariate sta-tistical methods (Section 3.5) All these amendments justify the change in the title of thebook to Solvents and Solvent E¤ects in Organic Chemistry

The references have been up-dated to cover literature appearing up to the firstpart of 1987 New references were added to the end of the respective reference list ofeach chapter from the first edition

Consistent use of the nomenclature, symbols, terms, and SI units recommended

I am very indebted to many colleagues for corrections, comments, and valuablesuggestions Especially helpful suggestions came from Professors H.-D Fo¨rsterling,Marburg, J Shorter, Hull/England, and R I Zalewski, Poznan´/Poland, to whom I amvery grateful For critical reading of the whole manuscript and the improvement of myEnglish I again thank Dr Edeline Wentrup-Byrne, now living in Brisbane/Australia

Dr P.-V Rinze, Marburg, and his son Lars helped me with the author index Finally,

I would like to thank my wife Maria for her sympathetic assistance during the tion of this edition and for her help with the indices

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

* Cf Pure Appl Chem 51, 1 (1979); ibid 53, 753 (1981); ibid 55, 1281 (1983); ibid 57, 105 (1985).

The organic chemist usually works with compounds which possess labile covalentbonds and are relatively involatile, thereby often rendering the gas-phase unsuitable as areaction medium Of the thousands of reactions known to occur in solution only fewhave been studied in the gas-phase, even though a description of reaction mechanisms ismuch simpler for the gas-phase The frequent necessity of carrying out reactions in thepresence of a more or less inert solvent results in two main obstacles: The reactiondepends on a larger number of parameters than in the gas-phase Consequently, theexperimental results can often be only qualitatively interpreted because the state ofaggregation in the liquid phase has so far been insu‰ciently studied On the other hand,the fact that the interaction forces in solution are much stronger and more varied than inthe gas-phase, permits to a¤ect the properties and reactivities of the solute in manifoldmodes.

Thus, whenever a chemist wishes to carry out a chemical reaction he not only has

to take into consideration the right reaction partners, the proper reaction vessels, andthe appropriate reaction temperature One of the most important features for the success

of the planned reaction is the selection of a suitable solvent Since solvent e¤ects onchemical reactivity have been known for more than a century, most chemists are nowfamiliar with the fact that solvents may have a strong influence on reaction rates andequilibria Today, there are about three hundred common solvents available, nothing tosay of the infinite number of solvent mixtures Hence the chemist needs, in addition tohis intuition, some general rules and guiding-principles for this often di‰cult choice.The present book is based on an earlier paperback ‘‘Lo¨sungsmittele¤ekte in derorganischen Chemie’’ [1], which, though following the same layout, has been completelyrewritten, greatly expanded, and brought up to date The book is directed both towardthe industrial and academic chemist and particularly the advanced student of chemistry,who on the one hand needs objective criteria for the proper choice of solvent but on theother hand wishes to draw conclusions about reaction mechanisms from the observedsolvent e¤ects

A knowledge of the physico-chemical principles of solvent e¤ects is required forproper bench-work Therefore, a description of the intermolecular interactions betweendissolved molecules and solvent is presented first, followed by a classification of solventsderived therefrom Then follows a detailed description of the influence of solvents onchemical equilibria, reaction rates, and spectral properties of solutes Finally, empiricalparameters of solvent polarity are given, and in an appendix guidelines to the everydaychoice of solvents are given in a series of Tables and Figures

The number of solvent systems and their associated solvent e¤ects examined is

so enormous that a complete description of all aspects would fill several volumes Forexample, in Chemical Abstracts, volume 85 (1976), approximately eleven articles perweek were quoted in which the words ‘‘Solvent e¤ects on ’’ appeared in the title Inthe present book only a few important and relatively well-defined areas of generalimportance have been selected The book has been written from the point of view ofpractical use for the organic chemist rather than from a completely theoretical one

In the selection of the literature more recent reviews were taken into accountmainly Original papers were cited in particular from the didactic point of view rather

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

than priority, importance or completeness This book, therefore, does not only have thecharacter of a monograph but also to some extent that of a textbook In order to helpthe reader in his use of the literature cited, complete titles of the review articles quotedare given The literature up until December 1977 has been considered together with afew papers from 1978 The use of symbols follows the recommendations of the SymbolsCommittee of the Royal Society, London, 1971 [2].

I am very grateful to Professor Karl Dimroth, Marburg, who first stimulated myinterest in solvent e¤ects in organic chemistry I am indebted to Professors W H Pirkle,Urbana/Illinois, D Seebach, Zu¨rich/Switzerland, J Shorter, Hull/England, and numer-ous other colleagues for helpful advice and information Thanks are also due to theauthors and publishers of copyrighted materials reproduced with their permission(cf Figure and Table credits on page 495) For the careful translation and improvement

of the English manuscript I thank Dr Edeline Wentrup-Byrne, Marburg Without theassistance and patience of my wife Maria, this book would not have been written

References

[1] C Reichardt: Lo¨sungsmittele¤ekte in der organischen Chemie 2 nd edition Verlag Chemie, Weinheim 1973;

E¤ets de solvant en chimie organique (translation of the first-mentioned title into French, by

I Tkatchenko), Flammarion, Paris 1971;

Rastvoriteli v organicheskoi khimii (translation of the first-mentioned title into Russian, by E R Zakhsa), Izdatel’stvo Khimiya, Leningrad 1973.

[2] Quantities, Units, and Symbols, issued by The Symbols Committee of the Royal Society, don, in 1971.

Lon-1 Introduction 1

2 Solute-Solvent Interactions 7

2.1 Solutions 7

2.2 Intermolecular Forces 12

2.2.1 Ion-Dipole Forces 13

2.2.2 Dipole-Dipole Forces 14

2.2.3 Dipole-Induced Dipole Forces 15

2.2.4 Instantaneous Dipole-Induced Dipole Forces 16

2.2.5 Hydrogen Bonding 17

2.2.6 Electron-Pair Donor/Electron-Pair Acceptor Interactions (EPD/EPA Interactions) 23

2.2.7 Solvophobic Interactions 31

2.3 Solvation 34

2.4 Preferential Solvation 43

2.5 Micellar Solvation (Solubilization) 48

2.6 Ionization and Dissociation 52

3 Classification of Solvents 65

3.1 Classification of Solvents according to Chemical Constitution 65

3.2 Classification of Solvents using Physical Constants 75

3.3 Classification of Solvents in Terms of Acid-Base Behaviour 88

3.3.1 Brønsted-Lowry Theory of Acids and Bases 88

3.3.2 Lewis Theory of Acids and Bases 93

3.4 Classification of Solvents in Terms of Specific Solute/Solvent Interactions 96

3.5 Classification of Solvents using Multivariate Statistical Methods 99

4 Solvent E¤ects on the Position of Homogeneous Chemical Equilibria 107

4.1 General Remarks 107

4.2 Solvent E¤ects on Acid/Base Equilibria 109

4.2.1 Brønsted Acids and Bases in Solution 109

4.2.2 Gas-Phase Acidities and Basicities 114

4.3 Solvent E¤ects on Tautomeric Equilibria 121

4.3.1 Solvent E¤ects on Keto/Enol Equilibria 121

4.3.2 Solvent E¤ects on Other Tautomeric Equilibria 128

4.4 Solvent E¤ects on Other Equilibria 136

4.4.1 Solvent E¤ects on Brønsted Acid/Base Equilibria 136

4.4.2 Solvent E¤ects on Lewis Acid/Base Equilibria 138

4.4.3 Solvent E¤ects on Conformational Equilibria 142

4.4.4 Solvent E¤ects on cis/trans or E/Z Isomerization Equilibria 148

4.4.5 Solvent E¤ects on Valence Isomerization Equilibria 150

4.4.6 Solvent E¤ects on Electron-Transfer Equilibria 153

4.4.7 Solvent E¤ects on Host/Guest Complexation Equilibria 156

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

5 Solvent E¤ects on the Rates of Homogeneous Chemical Reactions 165

5.1 General Remarks 165

5.2 Gas-Phase Reactivities 173

5.3 Qualitative Theory of Solvent E¤ects on Reaction Rates 180

5.3.1 The Hughes–Ingold Rules 181

5.3.2 Solvent E¤ects on Dipolar Transition State Reactions 192

5.3.3 Solvent E¤ects on Isopolar Transition State Reactions 206

5.3.4 Solvent E¤ects on Free-Radical Transition State Reactions 220

5.3.5 Limitations of the Hughes–Ingold Rules 235

5.4 Quantitative Theories of Solvent E¤ects on Reaction Rates 239

5.4.1 General Remarks 239

5.4.2 Reactions between Neutral, Apolar Molecules 240

5.4.3 Reactions between Neutral, Dipolar Molecules 246

5.4.4 Reactions between Neutral Molecules and Ions 254

5.4.5 Reactions between Ions 255

5.5 Specific Solvation E¤ects on Reaction Rates 259

5.5.1 Influence of Specific Anion Solvation on the Rates of SNand other Reactions 259

5.5.2 Protic and Dipolar Aprotic Solvent E¤ects on the Rates of SN Reactions 265

5.5.3 Quantitative Separation of Protic and Dipolar Aprotic Solvent E¤ects for Reaction Rates by Means of Solvent-Transfer Activity Coe‰cients 277 5.5.4 Acceleration of Base-Catalysed Reactions in Dipolar Aprotic Solvents 282 5.5.5 Influence of Specific Cation Solvation on the Rates of SN Reactions 285

5.5.6 Solvent Influence on the Reactivity of Ambident Anions 292

5.5.7 Solvent E¤ects on Mechanisms and Stereochemistry of Organic Reactions 298

5.5.8 Influence of Micellar and Solvophobic Interactions on Reaction Rates and Mechanisms 317

5.5.9 Liquid Crystals as Reaction Media 326

5.5.10 Solvent Cage E¤ects 331

5.5.11 External Pressure and Solvent E¤ects on Reaction Rates 336

5.5.12 Solvent Isotope E¤ects 343

5.5.13 Reactions in Biphasic Solvent Systems and in Neoteric Solvents 345

6 Solvent E¤ects on the Absorption Spectra of Organic Compounds 359

6.1 General Remarks 359

6.2 Solvent E¤ects on UV/Vis Spectra 360

6.2.1 Solvatochromic Compounds 360

6.2.2 Theory of Solvent E¤ects on UV/Vis Absorption Spectra 371

6.2.3 Specific Solvent E¤ects on UV/Vis Absorption Spectra 380

6.2.4 Solvent E¤ects on Fluorescence Spectra 384

6.2.5 Solvent E¤ects on ORD and CD Spectra 393

6.3 Solvent E¤ects on Infrared Spectra 397

6.4 Solvent E¤ects on Electron Spin Resonance Spectra 403

6.5 Solvent E¤ects on Nuclear Magnetic Resonance Spectra 410

6.5.1 Nonspecific Solvent E¤ects on NMR Chemical Shifts 410

6.5.2 Specific Solvent E¤ects on NMR Chemical Shifts 417

6.5.3 Solvent E¤ects on Spin-Spin Coupling Constants 422

7 Empirical Parameters of Solvent Polarity 425

7.1 Linear Gibbs Energy Relationships 425

7.2 Empirical Parameters of Solvent Polarity from Equilibrium Measurements 432

7.3 Empirical Parameters of Solvent Polarity from Kinetic Measurements 438 7.4 Empirical Parameters of Solvent Polarity from Spectroscopic Measurements 448

7.5 Empirical Parameters of Solvent Polarity from Other Measurements 481

7.6 Interrelation and Application of Solvent Polarity Parameters 483

7.7 Multiparameter Approaches 490

8 Solvents and Green Chemistry 509

8.1 Green Chemistry 509

8.2 Reduction of Solvent Use 511

8.3 Green Solvent Selection 513

8.4 Non-Traditional Solvents 514

8.4.1 Water 514

8.4.2 Supercritical Carbon Dioxide (sc-CO2) 529

8.4.3 Ionic Liquids 534

8.4.4 Polyethylene Glycols (PEGs) 543

8.4.5 Biomass-Derived Solvents 544

8.5 Outlook 548

Appendix 549

A Properties, Purification, and Use of Organic Solvents 549

A.1 Physical Properties 549

A.2 Purification of Organic Solvents 556

A.3 Spectroscopic Solvents 557

A.4 Solvents as Reaction Media 562

A.5 Solvents for Recrystallization 563

A.6 Solvents for Extraction and Partitioning (Distribution) 570

A.7 Solvents for Adsorption Chromatography 572

A.8 Solvents for Acid/Base Titrations in Non-Aqueous Media 574

A.9 Solvents for Electrochemistry 578

A.10 Toxicity of Organic Solvents 578

References 587

Figure and Table Credits 675

Subject Index 677

Abbreviations and Recommended Values of Some Fundamental Constants andNumbersa,b)

[¼ 1=ðm0
c0 Þ; m0¼ permeability ofvacuum]

22.711 L
mol1

Abbreviations and Symbols for Unitsa,b)

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

a) E R Cohen, T Cvitasˇ, J G Frey, B Holmstro¨m, K Kuchitsu, R Marquardt, I Mills,

F Pavese, M Quack, J Stohner, H L Strauss, M Takami, and A J Thor: Quantities, Units and Symbols in Physical Chemistry (IUPAC 2007), 3 rd ed., Royal Society of Chemistry, Cambridge, 2007.

b) G H Aylward and T J V Findlay: SI Chemical Data, 6 th ed., Wiley, Milton/Australia, 2008; see also Bureau International des Poids et Mesures (BIPM): Le Syste`me International d’Unite´s (SI), 8 th ed., STEDI, Paris, 2006.

cm3 cubic centimetre

(millilitre mL; 106m3)

volume

(magnetic field)

(Gutmann and Meyer)

or polarizability volume

C2
m2
J1or 4pe

0
cm3

hydrogen-bond donor acidity (Taftand Kamlet)

basicity (Palm and Koppel)

c) P Mu¨ller: Glossary of Terms used in Physical Organic Chemistry – IUPAC Recommendations

1994 Pure Appl Chem 66, 1077 (1994).

BMeOD IR based empirical parameter of

solvent Lewis basicity (Palm andKoppel)

solvent Lewis basicity (Koppel andPaju; Makitra)

tendency or ‘basity’ (Swain)

hydrogen-bond acceptor basicity(Taft and Kamlet)

density) of a solvent

parameter (Drago)

bond between H and A

kJ
mol1

basicity, based on a 1,3-dipolarcycloaddition reaction (Nagai et al.)

kcal
mol1

(Marcus)

(Taft and Kamlet)

acidity (Palm and Koppel)

parameter (Drago)

absorption of an aminyloxide radical(Mukerjee; Wrona)

EK empirical solvent polarity parameter,

molybdenum complex (Walther)

kcal
mol1

tungsten complex (Lees)

molar electronic excitation energy

kJ
mol1or kcal
mol1

based on the intramolecular CTabsorption of a pyridinium-N-phenolate betaine dye (Dimroth andReichardt)

kcal
mol1

parameter (Reichardt)

S-oxide (Walter)

kcal
mol1

(‘‘dielectric constant’’)

1

ketones (Dubois)

parameter (Schleyer and Allerhand)

kJ
mol1

H0 acidity function (Hammett)

(¼ 1/2
Pci
zi2)

mol
L1

(Kova´ts)

reactions

(L
mol1)n 1
s1

in the gas phase for monomolecular

(L
mol1)n 1
s1

constant of unsubstituted substrates

(L
mol1)n1
s1with

(mol
L1)Sv

(Hansch and Leo)

parameter of substituents (Menger)

(Marcus)

m permanent electric dipole moment of

at infinite dilution

kJ
mol1

(¼ c0=c)

nucleophilicity (Winstein andGrunwald)

(Ritchie)

inert reference solvent

Hz, s1

based on a Diels-Alder reaction(Berson)

bar (¼ 105Pa)

(Palm and Koppel)

(Taft)

pyrene (Winnik)

(Hansch and Leo)

lg a(H3Oþ)abbreviation of potentia or pondushydrogenii, power of hydrogen, orpuissance d’hydroge`ne (Sørensen1909) The pH scale ranges usuallyfrom 1 to 14, but is open-ended,allowing for pH values below 0 orabove 14!

pK lg K

polarizability parameter, based

substituted aromatics (Taft andKamlet)

polarizability parameter, based on the

constants

based on the Z-values (Brownstein)

tri-n-propylamine with iodomethane(Drougard and Decroocq)

(Abraham)

hydrogen-bond donor acidity(Catala´n)

hydrogen-bond acceptor basicity(Catala´n)

dipolarity/polarizability, based on the

7-nitrofluorenes (Catala´n)

amount-of-substance fraction

1

Nasielski)

merocyanine dyes (Brooker)

kcal
mol1

OyS

X;WyS

the transfer of a solute X from areference solvent (O) or water (W) toanother solvent (S)

ionizing power, based on t-butylchloride solvolysis (Winstein andGrunwald)

ionizing power, based on 2-adamantyltosylate solvolysis (Schleyer andBentley)

based on the intermolecular CTabsorption of a substitutedpyridinium iodide (Kosower)

kcal
mol1

satis excusserimus ea quatuor Instrumenta artis, et naturae, quae modo relinquimus,videamus quintum genus horum, quod ipsi Chemiae fere proprium censetur, cui certeChemistae principem locum prae omnibus assignant, in quo se jactant, serioque tri-umphant, cui artis suae, prae aliis omnibus e¤ectus mirificos adscribunt Atque illud

Hermannus Boerhaave (1668–1738)

De menstruis dictis in chemia, in:Elementa Chemiae (1733) [1, 2]

1 Introduction

The development of our knowledge of solutions reflects to some extent the development

of chemistry itself [3] Of all known substances, water was the first to be considered as asolvent As far back as the time of the Greek philosophers there was speculation aboutthe nature of solution and dissolution The Greek alchemists considered all chemicallyactive liquids under the name ‘‘Divine water’’ In this context the word ‘‘water’’ wasused to designate everything liquid or dissolved The Greek philosopher Thales of

and into everything resolved itself

From these ancient times, a familiar and today often cited quotation of the

Corpora non agunt nisi fluida (or liquida) seu soluta, and was translated into English as

‘‘Compounds do not react unless fluid or if dissolved’’ [43] However, according toHedvall [44], this seems to be a misinterpretation of the original text given in Greek asTa´ n´gra´ mikta´ ma´lista ton soma´ton (Ta hygra mikta malista ton somaton), which isprobably taken from Aristotle’s work De Generatione et Corruptione [45] According toHedvall, this statement should be better read as „ it is chiefly the liquid substanceswhich react’’ [44] or „ for instance liquids are the type of bodies most liable to mix-ing’’ [45c] In this somewhat softened version, Aristotle’s statement is obviously lessdistinct and didactic With respect of the many solid/solid reactions known today, it isquite understandable that solid-state chemists were not very happy with the commonfirst version of Aristotle’s statement [43, 44]

The alchemist’s search for a universal solvent, the so-called ‘‘Alkahest’’ or struum universale’’, as it was called by Paracelsus (1493–1541), indicates the impor-tance given to solvents and the process of dissolution Although the eager search of

‘‘Men-Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

* ‘‘Well then, my dear listeners, let us proceed with fervor to another problem! Having su‰ciently analyzed in this manner the four resources of science and nature, which we are about to leave (i.e fire, water, air, and earth) we must consider a fifth element which can almost be considered the most essential part of chemistry itself, which chemists boastfully, no doubt with reason, prefer above all others, and because of which they triumphantly celebrate, and to which they attribute above all others the marvellous e¤ects of their science And this they call the solvent (menstruum).’’

the chemists of the 15th to 18th centuries did not in fact lead to the discovery of any

‘‘Alkahest’’, the numerous experiments performed led to the uncovering of new solvents,

chem-ical rule that ‘‘like dissolves like’’ (similia similibus solvuntur) However, at that time,the words solution and dissolution comprised all operations leading to a liquid productand it was still a long way to the conceptual distinction between the physical dissolution

of a salt or of sugar in water, and the chemical change of a substrate by dissolution, forexample, of a metal in an acid Thus, in the so-called chemiatry period (iatrochemistryperiod), it was believed that the nature of a substance was fundamentally lost upon dis-solution Van Helmont (1577–1644) was the first to strongly oppose this contention Heclaimed that the dissolved substance had not disappeared, but was present in the solu-tion, although in aqueous form, and could be recovered [4] Nevertheless, the dissolution

of a substance in a solvent remained a rather mysterious process The famous Russianpolymath Lomonosov (1711–1765) wrote in 1747: ‘‘Talking about the process of disso-lution, it is generally said that all solvents penetrate into the pores of the body to bedissolved and gradually remove its particles However, concerning the question of whatforces cause this process of removal, there does not exist any somehow reasonableexplanation, unless one arbitrarily attributes to the solvents sharp wedges, hooks or,who knows, any other kind of tools’’ [27]

The further development of modern solution theory is connected with three sons, namely the French researcher Raoult (1830–1901) [28], the Dutch physical chemistvan’t Ho¤ (1852–1911) [5], and the Swedish scientist Arrhenius (1859–1927) [6] Raoultsystematically studied the e¤ects of dissolved nonionic substances on the freezing andboiling point of liquids and noticed in 1886 that changing the solute/solvent ratio pro-duces precise proportional changes in the physical properties of solutions The observa-tion that the vapour pressure of solvent above a solution is proportional to the molefraction of solvent in the solution is today known as Raoult’s law [28]

per-The di‰culty in explaining the e¤ects of inorganic solutes on the physical erties of solutions led in 1884 to Arrhenius’ theory of incomplete and complete dissoci-ation of ionic solutes (electrolytes, ionophores) into cations and anions in solution,which was only very reluctantly accepted by his contemporaries Arrhenius derived hisdissociation theory from comparison of the results obtained by measurements of elec-troconductivity and osmotic pressure of dilute electrolyte solutions [6]

prop-The application of laws holding for gases to solutions by replacing pressure byosmotic pressure was extensively studied by van’t Ho¤, who made osmotic pressuremeasurements another important physicochemical method in studies of solutions [5].The integration of these three basic developments established the foundations ofmodern solution theory and the first Nobel prizes in chemistry were awarded to van’tHo¤ (in 1901) and Arrhenius (in 1903) for their work on the osmotic pressure and thetheory of electrolytic dissociation in dilute solutions, respectively

The further development of solution chemistry is connected with the pioneeringwork of Ostwald (1853–1932), Nernst (1864–1941), Lewis (1875–1946), Debye (1884–

* Even if the once famous scholar J B Van Helmont (1577–1644) claimed to have prepared this

‘‘Alkahest’’ in a phial, together with the adherents of the alkahest theory he was ridiculed by his contemporaries who asked in which vessel he has stored this universal solvent.

1966), E Hu¨ckel (1896–1980), and Bjerrum (1879–1958) More detailed reviews on thedevelopment of modern solution chemistry can be found in references [29, 30].

The influence of solvents on the rates of chemical reactions [7, 8] was first noted

by Berthelot and Pe´an de Saint-Gilles in 1862 in connection with their studies on theesterification of acetic acid with ethanol: ‘‘ l’e´the´rification est entrave´e et ralentie parl’emploi des dissolvants neutres e´trangers a` la re´action’’ [9]*) After thorough studies onthe reaction of trialkylamines with haloalkanes, Menschutkin in 1890 concluded that areaction cannot be separated from the medium in which it is performed [10] In a letter

to Prof Louis Henry he wrote in 1890: ‘‘Or, l’expe´rience montre que ces dissolvantsexercent sur la vitesse de combinaison une influence conside´rable Si nous repre´sentonspar 1 la constante de vitesse de la re´action pre´cite´e dans l’hexane C6H14, cette constante

847.7 La di¤e´rence est e´norme, mais, dans ce cas, elle n’atteint pas encore le mum Vous voyez que les dissolvants, soi-disant indi¤e´rents ne sont pas inertes; ilsmodifient profonde´ment l’acte de la combinaison chimique Cet e´nonce´ est riche en

dis-covered that, in reactions between liquids, one of the reaction partners may constitute anunfavourable solvent Thus, in the preparation of acetanilide, it is not without impor-tance whether aniline is added to an excess of acetic acid, or vice versa, since aniline inthis case is an unfavourable reaction medium Menschutkin related the influence of sol-vents primarily to their chemical, not their physical properties

The influence of solvents on chemical equilibria was discovered in 1896,

com-pounds (Claisen [14]: acetyl-dibenzoylmethane and tribenzoylmethane; Wislicenus [15]:methyl and ethyl formylphenylacetate; Knorr [16]: ethyl dibenzoylsuccinate andethyl diacetylsuccinate) and the nitro-isonitro tautomerism of primary and secondarynitro compounds (Hantzsch [17]: phenyl-nitromethane) Thus, Claisen wrote: ‘‘Es gibt

* ‘‘ the esterification is disturbed and decelerated on addition of neutral solvents not belonging

to the reaction’’ [9].

** ‘‘Now, experience shows that solvents exert considerable influence on reaction rates If we resent the rate constant of the reaction to be studied in hexane C 6 H 14 by 1, then, all else being equal, this constant for the same reaction in CH 3 aaCOaaC 6 H 5 will be 847.7 The increase is enor- mous, but in this case it has not even reached its maximum So you see that solvents, in spite of appearing at first to be indi¤erent, are by no means inert; they can greatly influence the course of chemical reactions This statement is full of consequences for the chemical theory of dissolutions’’ [26].

rep-*** The first observation of a tautomeric equilibrium was made in 1884 by Zincke at Marburg [11] He observed that, surprisingly, the reaction of 1,4-naphthoquinone with phenylhydrazine gives the same product as that obtained from the coupling reaction of 1-naphthol with benzenediazonium salts This phenomenon, that the substrate can react either as phenylhydrazone or as a hydroxyazo compound, depending on the reaction circumstances, was called Ortsisomerie by Zincke [11] Later

on, the name tautomerism, with a di¤erent meaning however from that accepted today, was introduced by Laar [12] For a description of the development of the concept of tautomerism, see Ingold [13].

der Temperatur, bei den gelo¨sten Substanzen auch von der Art des Lo¨sungsmittels ha¨ngt

es ab, welche von den beiden Formen die besta¨ndigere ist’’ [14]*) The study of the enol equilibrium of ethyl formylphenylacetate in eight solvents led Wislicenus to theconclusion that the keto form predominates in alcoholic solution, the enol form in tri-chloromethane or benzene He stated that the final ratio in which the two tautomericforms coexist must depend on the nature of the solvent and on its dissociating power,whereby he suggested that the dielectric constants were a possible measure of this

keto-‘‘power’’ Stobbe was the first to review these results [18] He divided the solventsinto two groups according to their ability to isomerize tautomeric compounds His clas-sification reflects, to some extent, the modern division into protic and aprotic solvents.The e¤ect of solvent on constitutional and tautomeric isomerization equilibria waslater studied in detail by Dimroth [19] (using triazole derivatives, e.g 5-amino-4-methoxycarbonyl-1-phenyl-1,2,3-triazole) and Meyer [20] (using ethyl acetoacetate)

It has long been known that UV/Vis absorption spectra may be influenced bythe phase (gas or liquid) and that the solvent can bring about a change in the position,

sol-vent property led Kundt in 1878 to propose the rule, later named after him, thatincreasing dispersion (i.e increasing index of refraction) is related to a shift of theabsorption maximum towards longer wavelength [23] This he established on the basis

of UV/Vis absorption spectra of six dyestu¤s, namely chlorophyll, fuchsin, anilinegreen, cyanine, quinizarin, and egg yolk in twelve di¤erent solvents The – albeit limited– validity of Kundt’s rule, e.g found in the cases of 4-hydroxyazobenzene [24] and ace-tone [25], led to the realization that the e¤ect of solvent on dissolved molecules is a result

of electrical fields These fields in turn originate from the dipolar properties of the ecules in question [25] The similarities in the relationships between solvent e¤ects onreaction rate, equilibrium position, and absorption spectra has been related to the gen-eral solvating ability of the solvent in a fundamental paper by Scheibe et al [25].More recently, research on solvents and solutions has again become a topic ofinterest because many of the solvents commonly used in laboratories and in the chemicalindustry are considered as unsafe for reasons of environmental protection On the list ofdamaging chemicals, solvents rank highly because they are often used in huge amountsand because they are volatile liquids that are di‰cult to contain Therefore, the intro-duction of cleaner technologies has become a major concern throughout both academiaand industry [31–34] This includes the development of environmentally benign new

constitut-ing a class of novel solvents with desirable, less hazardous, new properties [35, 36] The

* ‘‘There are compounds capable of existence in the form aaC(OH)bbCaaaaCOaa as well as in the form aaCOaaCaaH aaCOaa; it depends on the nature of the substituents, the temperature, and for dissolved compounds, also on the nature of the solvent, which of the two forms will be the more stable’’ [14].

** A survey of older works of solvent e¤ects on UV/Vis absorption spectra has been given by Sheppard [21].

*** It should be noted that the now generally accepted meaning of the term solvatochromism fers from that introduced by Hantzsch (cf Section 6.2).

dif-term neoteric solvents covers supercritical fluids, ionic liquids, and also carbons (as used in fluorous biphasic systems) In addition, water, often consideredincompatible with organic synthesis, in recent decades has attracted increasing interest

perfluorohydro-as an environmentally benign and cheap solvent for a multitude of organic reactions[46] Table A-14 in Chapter A.10 (Appendix) collects some recommendations for thesubstitution of hazardous solvents, together with the relevant literature references; seealso Chapter 8

For the development of a sustainable chemistry based on clean technologies, thebest solvent would be no solvent at all For this reason, considerable e¤orts haverecently been made to design reactions that proceed under solvent-free conditions, usingmodern techniques such as reactions on solid mineral supports (alumina, silica, clays),solid-state reactions without any solvent, support, or catalyst between neat reactants,solid-liquid phase-transfer catalysed and microwave-activated reactions, as well as gas-phase reactions [37–42] A representative recent example of a highly e‰cient solvent-free organic synthesis is the (S)-proline-catalysed stereoselective aldol reaction betweencyclohexanone and 4-nitrobenzaldehyde, applying a very simple mechano-chemicaltechnique such as ball milling [42]

However, not all organic reactions can be carried out in the absence of a solvent;some organic reactions even proceed explosively in the solid state! Therefore, solventswill still be useful in mediating and moderating chemical reactions and this book onsolvent e¤ects will certainly not become superfluous in the foreseeable future

2.1 Solutions

In a limited sense solutions are homogeneous liquid phases consisting of more than onesubstance in variable ratios, when for convenience one of the substances, which is calledthe solvent and may itself be a mixture, is treated di¤erently from the other substances,which are called solutes [1] Normally, the component which is in excess is called thesolvent and the minor component(s) is the solute When the sum of the mole fractions ofthe solutes is small compared to unity, the solution is called a dilute solution*) A solu-tion of solute substances in a solvent is treated as an ideal dilute solution when the solute

that obey Raoult’s law over the entire composition range from pure A to pure B arecalled ideal solutions According to Raoult, the ratio of the partial pressure of compo-nent AðpAÞ to its vapour pressure as a pure liquid (p

A) is equal to the mole fraction of

AðxAÞ in the liquid mixture, i.e xA¼ pA=p

well, particularly when the components have a similar molecular structure (e.g benzeneand toluene)

A solvent should not be considered a macroscopic continuum characterized only

by its macroscopic physical constants such as boiling point, vapour pressure, density,cohesive pressure, index of refraction, relative permittivity, thermal conductivity, surfacetension, etc From the molecular-microscopic point of view, a solvent is a discontinuumwhich consists of individual, mutually interacting solvent molecules, characterized bytheir molecular properties such as dipole moment, electronic polarizability, hydrogen-bond donor (HBD) and hydrogen-bond acceptor (HBA) capability, electron-pair donor(EPD) and electron-pair acceptor (EPA) capability, etc According to the extent of theseintermolecular solvent/solvent interactions, there are highly structured solvents (e.g.,water with its strong directional hydrogen bonds, forming an intermolecular networkwith cavities) and less structured solvents (e.g., hydrocarbons with their weak nondirec-tional dispersion forces, filling the available space in a more regular manner) [173].The interactions between species in solvents (and in solutions) are at once toostrong to be treated by the laws of the kinetic theory of gases, yet too weak to be treated

by the laws of solid-state physics Thus, the solvent is neither an indi¤erent medium inwhich the dissolved material di¤uses in order to distribute itself evenly and randomly,nor does it possess an ordered structure resembling a crystal lattice Nevertheless, thelong-distance ordering in a crystal corresponds somewhat to the local ordering in a liq-uid Thus, neither of the two possible models – the gas and crystal models – can be ap-plied to solutions without limitation There is such a wide gulf between the two models

in terms of conceivable and experimentally established variants, that it is too di‰cult todevelop a generally valid model for liquids Due to the complexity of the interactions,the structure of liquids – in contrast to that of gases and solids – is the least-known ofall aggregation states Therefore, the experimental and theoretical examination of the

Solvents and Solvent Effects in Organic Chemistry, Fourth Edition Edited by Christian Reichardt and Thomas Welton Copyright 8 2011 WILEY-VCH Verlag GmbH & Co KGaA, Weinheim

* The superscript y attached to the symbol for a property of a solution denotes the property of an infinitely dilute solution.

structure of liquids is among the most di‰cult tasks of physical chemistry [2–7, 172–174].

Any theory of the liquid state has to explain – among others – the following facts:Except for water, the molar volume of a liquid is roughly 10% greater than that of thecorresponding solid According to X-ray di¤raction studies, a short-range order of sol-vent molecules persists in the liquid state and the nearest neighbour distances are almostthe same as those in the solid The solvent molecules are not moving freely, as in thegaseous state, but instead move in the potential field of their neighbours The potentialenergy of a liquid is higher than that of its solid by about 10% Therefore, the heat offusion is roughly 10% of the heat of sublimation Each solvent molecule has an envi-ronment very much like that of a solid, but some of the nearest neighbours are replaced

by holes Roughly one neighbour molecule in ten is missing

Even for the most important solvent – water – the investigation of its inner finestructure is still the subject of current research [8–15, 15a]*) Numerous di¤erent models,e.g the ‘‘flickering cluster model’’ of Franck and Wen [16], were developed to describethe structure of water However, all these models prove themselves untenable for acomplete description of the physico-chemical properties of water and an interpretation

of its anomalies [15, 304] Fig 2-1 should make clear the complexity of the inner ture of water

struc-Liquid water consists both of bound ordered regions of a regular lattice, andregions in which the water molecules are hydrogen-bonded in a random array; it is per-meated by monomeric water and interspersed with random holes, lattice vacancies, andcages There are chains and small polymers as well as bound, free, and trapped watermolecules [9, 15] The currently accepted view of the structure of liquid water treats it as

a dynamic three-dimensional hydrogen-bonded network, without a significant number

of non-bonded water molecules, that retains several of the structural characteristics ofice (i.e tetrahedral molecular packing with each water molecule hydrogen-bonded

to four nearest neighbours), although the strict tetrahedrality is lost Its dynamic haviour resembles that of most other liquids, with short rotational and translationalcorrelation times of the order of 0.1 to 10 ps, indicating high hydrogen-bond exchangerates [176, 305]

be-In principle, other hydrogen-bonded solvents should possess similar complicatedstructures [306] However, whereas water has been thoroughly studied [15, 17, 307], theinner structures of other solvents are still less well known [172, 177–179] By way ofexample, the intermolecular structure of acetone is determined mainly by steric inter-actions between the methyl groups and, unexpectedly, only to a small extent by dipole/dipole forces [308], whereas the inner structure of dimethyl sulfoxide is dictated bystrong dipole/dipole interactions [309] The inner structure of self-associated methanol isdominated by hydrogen-bonded ring clusters (preferentially hexamers; no chains) inwhich the monomers participate as both H-bond donor and acceptor [413]

* The amusing story of ‘‘polywater,’’ which excited the scientific community for a few years during the late 1960’s and early 1970’s, has been reviewed by Franks [175] It turned out that polywater was not a new and more stable form of pure water, but merely dirty water The strange properties

of polywater were due to high concentrations of siliceous material dissolved from quartz capillaries

in which it was produced.

Fig 2-1 Two-dimensional schematic diagram of the three-dimensional structure of liquid water [9].

From the idea that the solvent only provides an indi¤erent reaction medium,comes the Ruggli-Ziegler dilution principle, long known to the organic chemist Accord-ing to this principle, in the case of cyclization reactions, the desired intramolecularreaction will be favoured over the undesired intermolecular reaction by high dilutionwith an inert solvent [18, 310].

The assumption of forces of interaction between solvent and solute led, on theother hand, to the century-old principle that ‘‘like dissolves like’’ (similia similibus sol-vuntur), where the word ‘‘like’’ should not be too narrowly interpreted In many cases,the presence of similar functional groups in the molecules su‰ces When a chemicalsimilarity is present, the solution of the two components will usually have a structuresimilar to that of the pure materials (e.g alcohol-water mixtures [19]) This rule ofthumb has only limited validity, however, since there are many examples of solutions ofchemically dissimilar compounds For example, methanol and benzene, water and N,N-dimethylformamide, aniline and diethyl ether, and polystyrene and chloroform, are allcompletely miscible at room temperature On the other hand, insolubility can occur inspite of similarity of the two partners Thus, polyvinyl alcohol does not dissolve inethanol, acetyl cellulose is insoluble in ethyl acetate, and polyacrylonitrile is insoluble inacrylonitrile [20] Between these two extremes there is a whole range of possibilitieswhere the two materials dissolve each other to a limited extent The system water/diethylether is such an example Pure diethyl ether dissolves water to the extent of 15 mg/g at

two solvents is in large excess a homogeneous solution is obtained Two phases occurwhen the ratio is beyond the limits of solubility A more recent example of a rea‰rma-tion of the old ‘‘like dissolves like’’ rule is the di¤erential solubility of fullerene (C60),consisting of a three-dimensional delocalized 60p-electron system, in solvents such as

However, rather than the ‘‘like dissolves like’’ rule, it is the intermolecular action between solvent and solute molecules that determines the mutual solubility Acompound A dissolves in a solvent B only when the intermolecular forces of attraction

[21]

The sum of the interaction forces between the molecules of solvent and solute can

inter-actions A   A or B    B, respectively, as polar, and those with small interactions asnonpolar, four cases allowing a qualitative prediction of solubility can be distinguished(Table 2-1)

An experimental verification of these simple considerations is given by the bility data in Table 2-2

solu-The solubilities of ethane and methane are higher in nonpolar methane, whereas the opposite is true for chloromethane and dimethyl ether A survey

tetrachloro-of the reciprocal miscibility tetrachloro-of some representative examples tetrachloro-of organic solvents is given

Table 2-2 Solubilities of methane, ethane, chloromethane, and dimethyl ether in

tetrachloromethane (nonpolar solvent) and acetone (polar solvent) [22].

Solute Solute polarity Solubility/(mol  m 3) at 25C

Table 2-1 Solubility and polarity [22].

Solute A Solvent B Interaction

A    A B    B A    B

Solubility of

A in B

a) Not much change for solute or solvent.

b) Di‰cult to break up B    B.

c) Di‰cult to break up A    A.

a deeper and more detailed understanding of the diverse rules determining the solubility

of organic compounds in various solvents, see references [312–316]

The solubility parameter d of Hildebrand [4, 24], as defined in Eq (2-1), can often

be used in estimating the solubility of non-electrolytes in organic solvents

molar energy and the molar enthalpy (heat) of vaporization to a gas of zero pressure,respectively d is a solvent property which measures the work necessary to separate thesolvent molecules (i.e disruption and reorganization of solvent/solvent interactions) tocreate a suitably sized cavity, large enough to accommodate the solute Accordingly,highly ordered self-associated solvents exhibit relatively large d values (d¼ 0 for the gasphase) As a rule, it has been found that a good solvent for a certain non-electrolyte has

a d value close to that of the solute [20, 24, 25]; cf Table 3-3 in Section 3.2 for a tion of d values Often a mixture of two solvents, one having a d value higher and theother having a d value lower than that of the solute is a better solvent than each of thetwo solvents separately [24]; cf also Section 3.2

collec-A nice example demonstrating mutual insolubility due to di¤erent d values hasbeen described by Hildebrand [180], and was later improved [181] A system of eightnon-miscible liquid layers was constructed The eight layers in order of increasing den-sities are para‰n oil, silicone oil, water, aniline, perfluoro(dimethylcyclohexane), white

tem-perature is required to melt the gallium and phosphorus [181] A simplified, less harmfulversion with five colourless liquid phases consists of mineral (para‰n) oil, methyl sili-cone oil, water, benzyl alcohol, and perfluoro(N-ethylpiperidine) (or another perfluoro-organic liquid), in increasing order of density [317] Addition of an organic-soluble dyecan colour some of the five layers Even mixtures of some hydrophilic ionic liquids andsome specific hydrophobic ionic liquids can be immiscible and give rise to two phases Astable tetraphasic solvent mixture containing two immiscible ionic liquids is formed by(from top to bottom) n-pentane, tri(n-hexyl)-n-tetradecylphosphonium chloride, water,and 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide [414]

The complexity of multi-phasic liquid systems can be nicely demonstrated withthe following experiment, called ‘‘James-Bond-Cocktail’’ [452]: starting from n-per-fluoroheptane, a saturated aqueous potassium carbonate solution, methanol, and tol-uene (coloured with suitable dyes), a three-phase solvent system is obtained, which aftershaking (not stirring!) develops four layers; addition of n-pentane changes the sequence

of the two upper layers

2.2 Intermolecular Forces [26, 27, 182–184]

Intermolecular forces are those which can occur between closed-shell molecules [26, 27].These noncovalent interactions are also called van der Waals forces, since the Dutchscientist J D van der Waals recognized them (1873, in his PhD thesis) as the reason for

the non-ideal behaviour of real gases Intermolecular forces are usually classified intotwo distinct categories The first category comprises the so-called directional, induction,and dispersion forces, which are non-specific and cannot be completely saturated ( just

as Coulomb forces between ions cannot) The second group consists of bonding forces, and charge-transfer or electron-pair donor–acceptor forces The lattergroup are specific, directional forces, which can be saturated and lead to stoichiometricmolecular compounds For the sake of completeness, in the following the Coulombforces between ions and electrically neutral molecules (with permanent dipole moments)will be considered first, even though they do not belong to the intermolecular forces inthe narrower sense

hydrogen-2.2.1 Ion-Dipole Forces [28, 185]

Electrically neutral molecules with an unsymmetrical charge distribution possess a manent dipole moment m If the magnitude of the two equal and opposite charges of thismolecular dipole is denoted by q, and the distance of separation l, the dipole moment isgiven by m¼ q  l When placed in the electric field resulting from an ion, the dipole willorient itself so that the attractive end (the end with charge opposite to that of the ion)will be directed toward the ion, and the other repulsive end directed away The potentialenergy of an ion-dipole interaction is given by

per-Uion-dipole¼ 4p1 e

where e0is the permittivity of a vacuum, z e the charge on the ion, r the distance fromthe ion to the center of the dipole, and y the dipole angle relative to the line r joining

is positioned next to the ion in such a way that the ion and the separated charges of

Only molecules possessing a permanent dipole moment should be called dipolarmolecules Apart from a few hydrocarbons (n-hexane, cyclohexane, and benzene) andsome symmetrical compounds (carbon disulfide, tetrachloromethane, and tetra-chloroethene) all common organic solvents possess a permanent dipole moment of

Appendix, Table A-1, hexamethylphosphoric triamide is the one with the highest dipole

* It should be noted that Eqs (2-2) to (2-6) are valid only for gases; an exact application to tions is not possible Furthermore, Eqs (2-2) to (2-6) are restricted to cases with r g l.

solu-moment (m¼ 18:48  1030 Cm), followed by propylene carbonate (m¼ 16:7  1030

are exhibited by zwitterionic compounds such as the sydnones (i.e oxadiazolium-5-olates) For example, 4-ethyl-3-(1-propyl)sydnone, a high-boiling liquid(tbp¼ 155C/3 Torr) with a large relative permittivity (er¼ 64:6 at 25C), has a dipole

such room temperature liquid sydnones make them to good nonaqueous dipolar vents for many ionophores (electrolytes)

Ion-dipole forces are important for solutions of ionic compounds in dipolar vents, where solvated species such as Na(OH2)lm and Cl(H2O)mn (for solutions of NaCl

stable to be considered as discrete species, such as [Co(NH3)6]3lor Ag(CH3CN)l2 4.For a comprehensive review on ion/solvent interactions, see reference [241]

2.2.2 Dipole-Dipole Forces [29]

Directional forces depend on the electrostatic interaction between molecules possessing

a permanent dipole moment m due to their unsymmetrical charge distribution Whentwo dipolar molecules are optimally oriented with respect to one another at a distance r

as shown in Fig 2-3a, then the force of attraction is proportional to 1=r3 An alternativearrangement is the anti-parallel arrangement of the two dipoles as shown in Fig 2-3b.Unless the dipole molecules are very voluminous, the second arrangement is themore stable one The two situations exist only when the attractive energy is larger thanthe thermal energies Therefore, the thermal energy will normally prevent the dipolesfrom optimal orientation If all possible orientations were equally probable, that is, thedipoles correspond to freely rotating molecules, then attraction and repulsion wouldcompensate each other The fact that dipole orientations leading to attraction are sta-tistically favoured leads to a net attraction, which is strongly temperature dependent,

populated and the potential energy is zero This Boltzmann-averaged dipole/dipoleinteraction is usually referred to as the orientation or Keesom interaction [29] According

Among other interaction forces, these dipole-dipole interactions are mainlyresponsible for the association of dipolar organic solvents such as dimethyl sulfoxide [30]

or N,N-dimethylformamide [31]

It should be mentioned that dipoles represent only one possibility for the chargearrays in electric multipoles (n-poles) n-Poles with an array of point charges with an

Cl) A dipole (n¼ 2; e.g H2O, H3CaaCOaaCH3) is an array of partial charges with

dipole/dipole interactions, in solution there can also exist such higher intermolecularmultipole/multipole interactions Therefore, to some degree, octupolar tetrachloro-methane is also a kind of polar solvent However, the intermolecular interaction energyrapidly falls o¤ at higher orders of the multipole [26d] The anomalous behaviour of thechair-configured, non-dipolar solvent 1,4-dioxane, which often behaves like a polar sol-vent even though its relative permittivity is low (er¼ 2:2), is caused by its large nonidealquadrupolar charge distribution [411]

For the calculation of quadrupole moments for water and some organic solvents,which are experimentally not available, see reference [415]

2.2.3 Dipole-Induced Dipole Forces [32]

The electric dipole of a molecule possessing a permanent dipole moment m can induce

a dipole moment in a neighbouring molecule This induced moment always lies in thedirection of the inducing dipole Thus, attraction always exists between the two partners,

larger the electronic polarizability a of the apolar molecule experiencing the induction ofthe permanent dipole The net dipole/induced dipole energy of interaction for two dif-

polar-izabilities a1and a2, often referred to as the induction or Debye interaction [32], is given

elec-For a dipolar molecule of m¼ 3:3  1030Cm (1.0 D; e.g HaaCl) separated from amolecule of polarization volume a¼ 10  1030m3(e.g C6H6) by a distance of 300 pm,

Similarly, a charged particle such as an ion introduced into the neighbourhood of

an uncharged, apolar molecule will distort the electron cloud of this molecule in thesame way The polarization of the neutral molecule will depend upon its inherent

energy of such an interaction is given by Eq (2-5)

Uion-induced dipole¼  1

The importance of both of these interactions is limited to situations such as solutions ofdipolar or ionic compounds in nonpolar solvents

2.2.4 Instantaneous Dipole-Induced Dipole Forces [33, 34, 186]

Even in atoms and molecules possessing no permanent dipole moment, the continuouselectronic movement results, at any instant, in a small dipole moment m, which canfluctuatingly polarize the electron system of the neighbouring atoms or molecules Thiscoupling causes the electronic movements to be synchronized in such a way that amutual attraction results The energy of such so-called dispersion or London [33] inter-actions can be expressed as

potentials of the two di¤erent interacting species [33] When applied to two molecules ofthe same substance, Eq (2-6a) reduces to Eq (2-6b)

Udispersion¼  1

Dispersion forces are extremely short-range in action (depending on 1=r6!)

Dispersion forces are universal for all atoms and molecules; they alone areresponsible for the aggregation of molecules which possess neither free charges norelectric dipole moments Due to the greater polarizability of p-electrons, especiallystrong dispersion forces exist between molecules with conjugated p-electron systems (e.g.aromatic hydrocarbons) For many other dipole molecules with high polarizability aswell, the major part of the cohesion is due to dispersion forces For example, the calcu-

14% inductional energy, and 78% dispersion energy [35] Two molecules with

a¼ 3  1030 m3, I¼ 20  1019 J, and r¼ 3  1010 m have an interaction potential of

11.3 kJ/mol (2.7 kcal/mol) [35a] These values of a, I, and the average intermoleculardistance r correspond to those for liquid HCl It is instructive to compare the magnitude

of these dispersion forces with that of the dipole-dipole interactions For two dipoles,

are considerably stronger than the dipole-dipole forces of nearest neighbour distance inthe liquid state However, at larger distances the dispersion energy falls o¤ rapidly

As a result of the a2term in Eq (2-6b), dispersion forces increase rapidly with themolecular volume and the number of polarizable electrons The electronic polarizability

a is connected with the molar refraction and the index of refraction, according to theequation of Lorenz-Lorentz Therefore, solvents with a large index of refraction, andhence large optical polarizability, should be capable of enjoying particularly strong dis-persion forces As indicated in Table A-1 (Appendix), all aromatic compounds possess

refraction

The important role of inter- and intramolecular dispersion interactions in actions between aromatic molecules such as the photo-dimerization of anthracene in a

Solvents with high polarizability are often good solvators for anions which alsopossess high polarizability This is due to the fact that the dispersional interactionsbetween the solvents and the large, polarizable anions like Im3 , Im, SCNmor the picrateanion are significantly larger than for the smaller anions like Fm, HOm, or R2Nm[36].Perfluorohydrocarbons have unusually low boiling points because tightly held electrons

in fluorine have only a small polarizability

A remarkable example of the strength of dispersion interactions, taken from theanimal kingdom, will conclude this Section Geckos (family Geckonidae) are able toclimb rapidly up smooth vertical surfaces, and even to move upside down on a glassceiling The soles of their feet consist of hairy films, which a¤ord geckos the ability tostick to many di¤erent surfaces These extraordinary adhesion properties are due tostrong van der Waals forces, particularly dispersion interactions between millions ofextremely fine hairs (spatulae), providing a su‰ciently large surface area in close contactwith other surfaces This phenomenon has led to the gecko-inspired fabrication of hairypolymer films with unusual adhesion properties and wettability characteristics for avariety of organic solvents [438]

2.2.5 Hydrogen Bonding [26, 37–46, 187–190, 306]

Liquids possessing hydroxy groups or other groups with a hydrogen atom bound to anelectronegative atom X are strongly associated and have abnormal boiling points Thisobservation led to the contention that particular intermolecular forces apply here Theseare designated as hydrogen bridges, or hydrogen bonds, characterized by a coordinativedivalency of the hydrogen atom involved A general definition of the hydrogen bond is: