《有机化学》课程教学资源（参考书籍）Solvents and Solvent Effects in Organic Chemistry, Third, Updated and Enlarged Edition, 2003, Christian Reichardt

1Introduction 3 I'acte de la combinaison chimique Cet enonce est riche en consequences pour la theorie chimique des dissolutions"[26]*).Menschutkin also dis covered that,in reactions between liquids,one of the reaction partners may constitute an unfavourable 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 in this case is an unfavorable 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 simultaneously with the discovery of keto-enol tautomerism*in 1,3-dicarbonyl com pounds(Claisen [14]:acetyldibenzoylmethane and tribenzoylmethane;Wislicenus [15] methyl and ethyl formylphenylacetate:Knorr [16]:ethyl dibenzoylsuccinate and ethyl diacetylsuccinate)and the nitro-isonitro tautomerism of primary and secondary nitro compounds(Hantzsch [17]:phenylnitromethane).Thus,Claisen wrote:"Es gibt Verbindungen,welche sowohl in der Form-C(OH)-C-CO-wie in der Form -CO-CH-CO-zu bestehen vermogen;von der Natur der angelagerten Reste,von der Temperatur,bei den gelosten Substanzen auch von der Art des Losungsmittels hangt es ab,welche von den beiden Formen die bestandigere ist"[14]***.The study of the keto-enol equilibrium of ethyl formylphenylacetate in eight solvents led Wislicenus to the conclusion that the keto form predominates in alcoholic solution,the enol form in chloroform or benzene.He stated that the final ratio in which the two tautomeric forms coexist must depend on the nature of the solvent and on its dissociating power,whereby he suggested that the dielectric constants were a ssible measure of this"power Stobbe was the first to review these results 18).He divided the solvents into two g according to their ability to isomerize tautor eric compounds.His classification reflects to some extent,the modern division into protic and aprotic solvents.The effect of sol ent on constitutional and taut eric i as later studied in detail Now,experience shows that solvents ex tcoasid rable influen on rate we rep CeHs will bs 4. The e is eno s,but in this case it h s not even r ched its maximum So you s 【ha solvents,in spite c The first obse ade in 1884 by zir He obse ed that as that ob m the coupling re on of I-naphthol with b duced by Laar For m that accepted today.wa There are compounds capable of existence in the form-C(OH)=C-CO-as well as in the unds.also stable”[14

mum. . . . Vous voyez que les dissolvants, soi-disant indi¤e´rents ne sont pas inertes; ils modifient profonde´ment l’acte de la combinaison chimique. Cet e´nonce´ est riche en conse´quences pour la the´orie chimique des dissolutions’’ [26]*). Menschutkin also dis￾covered that, in reactions between liquids, one of the reaction partners may constitute an unfavourable 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 in this case is an unfavorable 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, simultaneously with the discovery of keto-enol tautomerism**) in 1,3-dicarbonyl com￾pounds (Claisen [14]: acetyldibenzoylmethane and tribenzoylmethane; Wislicenus [15]: methyl and ethyl formylphenylacetate; Knorr [16]: ethyl dibenzoylsuccinate and ethyl diacetylsuccinate) and the nitro-isonitro tautomerism of primary and secondary nitro compounds (Hantzsch [17]: phenylnitromethane). Thus, Claisen wrote: ‘‘Es gibt Verbindungen, welche sowohl in der Form aaC(OH)bbCaa aaCOaa wie in der Form aaCOaaCaa HaaCOaa zu bestehen vermo¨gen; von der Natur der angelagerten Reste, von 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 keto-enol equilibrium of ethyl formylphenylacetate in eight solvents led Wislicenus to the conclusion that the keto form predominates in alcoholic solution, the enol form in chloroform or benzene. He stated that the final ratio in which the two tautomeric forms 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 ‘‘power’’. Stobbe was the first to review these results [18]. He divided the solvents into two groups according to their ability to isomerize tautomeric compounds. His classification reflects, to some extent, the modern division into protic and aprotic solvents. The e¤ect of sol￾vent on constitutional and tautomeric isomerization equilibria was later studied in detail * ‘‘Now, experience shows that solvents exert considerable influence on reaction rates. If we rep￾resent the rate constant of the reaction to be studied in hexane C6H14 by 1, then, all else being equal, this constant for the same reaction in CH3 aaCOaaC6H5 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]. ** 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]. *** ‘‘There are compounds capable of existence in the form aaC(OH)bbCaa aaCOaa as well as in the form aaCOaaCaa HaaCOaa; 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]. 1 Introduction 3

4 1 Introduction 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 by the phase(gas or liquid)and that the solvent can bring about a change in the position. iensity.and shape of the absorption band Hantzsch later termed this phenomenon 1221.The search for a relationship between solvent effect and sol- vent property led Kundt in 1878 to propose the rule,later named after him,that increa dispersion (ie increasing index of refraction)is related to a shift of the maximum towards longe wavelength [231.This he stablished on the basis of UV/Vis absorption spectra of six dyestuffs.namely chlorophyll.fuchsin.aniline nizarin and ega volk i twelve different solver The albeit limited eg.found in the ases of 4-hydr ne 1241 and ace one [251.led to the re hat the eftec olved molecule of electrical fields.These fields in tur ate from the din of the cules in qu ion 1251 The similarities in the relationship nd abs ility of th po edto the gen t in a fund ptio by Sch et al as again of ecau of the d in lab che stry ai sidere fo the ons of en prot aging emicals hey are latile to con Th a ma he de solvents, times called neoter new,modern) ing a class of novel solvents with de ble,less hazard new properties 35,36]. s covers and also pe carbons (as used in fluorous biphasic systems). Table A-14 in Chapter A.10(Appendix collects some recommendations for the substitution of hazardous solvents,together with the relevant literature references For the development of a sustainable chemistry based on clean technologies,the best solvent would be no solvent at all.For this reason,considerable efforts have recently been made to design reactions that proceed under solvent-free conditions.using modern 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].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,solvents will still be useful in mediating and moderating chemical reactions and this book on solvent effects will certainly not become superfluous in the foreseeable future. A survey of older works of solvent effects on UV/Vis absorption spectra has been given by Sheppard omism differ

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 by the phase (gas or liquid) and that the solvent can bring about a change in the position, intensity, and shape of the absorption band*). Hantzsch later termed this phenomenon solvatochromism**) [22]. The search for a relationship between solvent e¤ect and sol￾vent property led Kundt in 1878 to propose the rule, later named after him, that increasing dispersion (i.e. increasing index of refraction) is related to a shift of the absorption maximum towards longer wavelength [23]. This he established on the basis of UV/Vis absorption spectra of six dyestu¤s, namely chlorophyll, fuchsin, aniline green, 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 mol￾ecules in question [25]. The similarities in the relationships between solvent e¤ects on reaction 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 of interest because many of the solvents commonly used in laboratories and in the chemical industry are considered as unsafe for reasons of environmental protection. On the list of damaging chemicals, solvents rank highly because they are often used in huge amounts and 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 academia and industry [31–34]. This includes the development of environmentally benign new solvents, sometimes called neoteric solvents (neoteric ¼ recent, new, modern), constitut￾ing a class of novel solvents with desirable, less hazardous, new properties [35, 36]. The term neoteric solvents covers supercritical fluids, ionic liquids, and also perfluorohydro￾carbons (as used in fluorous biphasic systems). Table A-14 in Chapter A.10 (Appendix) collects some recommendations for the substitution of hazardous solvents, together with the relevant literature references. For the development of a sustainable chemistry based on clean technologies, the best solvent would be no solvent at all. For this reason, considerable e¤orts have recently been made to design reactions that proceed under solvent-free conditions, using modern 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]. 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, solvents will still be useful in mediating and moderating chemical reactions and this book on solvent e¤ects will certainly not become superfluous in the foreseeable future. * 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 di¤ers from that introduced by Hantzsch (cf. Section 6.2). 4 1 Introduction

2 Solute-Solvent Interactions 2.1 Solutions In a limited sense solutions are homogeneous liquid phases consisting of more than ond substance in variable ratios.when for con nier of the substand which is called the solrent and may itself be a mixture is treated differently from the other substances hich are called solutes ill normally the which is in s is called the solvent and the (s)is the solute.When the sum of the d t nt the 11.171.Solu e/soly nt D A to B ar cording to R the parti es 6 A(PA) uid m as a pur (PA) re,I. PA bey Ra ult' w ver parti alarly when the compone nave a similar mo r structure (e.g.be nt should not be considered a macros continuum cha acterized only by such乙 cons which cons sts c f individua ally int ng s According to the extent or the are solven with a prono nternal structure (e.g.water)and others in which the interaction between the so ven s small (e.g.nyaroc bons).The interactions etween species in solv ents (an in solutions)are at once too strong t be treated by the laws of the kine gases,yet too weak to be treated by the laws of solid-state physics. Thus.the solvent is either an indifferent medium in which the dissolved material diffuses in order to dis tribute itself evenly and randomly,nor does it possess an ordered structure resembling a crystal lattice.Nevertheless,the long-distance ordering in a crystal corresponds some- what to the local ordering in a liquid.Thus.neither of the two possible models-the gas and crystal models-can be applied 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 difficult to develop 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 of all aggregation states.Therefore,the experimental and theoretical examination of the structure of liquids is among the most difficult tasks of physical chemistry [2-7,172-1741. 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 the corresponding solid.According to X-ray diffraction studies,a short-range order of sol- vent molecules persists in the liquid state and the nearest neighbour distances are almost the same as those in the solid.The solvent molecules are not moving freely,as in the ◆The sup to the symbol for a property of a solution denotes the property of an infinitely dilute solution. mbTdEo

2 Solute-Solvent Interactions 2.1 Solutions In a limited sense solutions are homogeneous liquid phases consisting of more than one substance in variable ratios, when for convenience one of the substances, which is called the 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 the solvent and the minor component(s) is the solute. When the sum of the mole fractions of the 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 activity coe‰cients g are close to unity (g ¼ 1) [1, 171]. Solute/solvent mixtures A þ B that obey Raoult’s law over the entire composition range from pure A to pure B are called 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. xA ¼ pA=p
A. Many mixtures obey Raoult’s law very well, particularly when the components have a similar molecular structure (e.g. benzene and toluene). A solvent should not be considered a macroscopic continuum characterized only by physical constants such as density, dielectric constant, index of refraction etc., but as a discontinuum which consists of individual, mutually interacting solvent molecules. According to the extent of these interactions, there are solvents with a pronounced internal structure (e.g. water) and others in which the interaction between the solvent molecules is small (e.g. hydrocarbons). The interactions between species in solvents (and in solutions) are at once too strong 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 in which the dissolved material di¤uses in order to dis￾tribute itself evenly and randomly, nor does it possess an ordered structure resembling a crystal lattice. Nevertheless, the long-distance ordering in a crystal corresponds some￾what to the local ordering in a liquid. Thus, neither of the two possible models – the gas and crystal models – can be applied 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 to develop 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 of all aggregation states. Therefore, the experimental and theoretical examination of the 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 the corresponding 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 almost the same as those in the solid. The solvent molecules are not moving freely, as in the * The superscript y attached to the symbol for a property of a solution denotes the property of an infinitely dilute solution. Solvents and Solvent Effects in Organic Chemistry, Third Edition. Christian Reichardt Copyright 8 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 3-527-30618-8

6 2 Solute-Solvent Interactions gaseous state,but instead move in the potential field of their neighbours.The potential energy of a liquid is higher than that of its solid by about 10%.Therefore,the heat of fusion 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 fine structure is still the subiect of current research 18-15.15al*Nume rous different models ea the"Alickering cluster model of franck and Wen [161 were developed to describe the structure of water.However.all these models p ve the selves ntenable for complete description of the physico-chemical properties of water and an interpretati of its anomalies 304].Fig.2-1 should make clear the complexity of the inner structur of water liquid water consists both of bound ordered reg ons of a r gular lattic regions in which the tater molecule n array;it is eated by mo and inte ndom holes latti chains and ell as b app 61 The cepte str er treat ret the (ie P on alt the st 17 Its tiona anslat es of the order of 0.1 to 10 ps,indicating high hydrogen-b d exchange rates [176,30 ple other hydrogen-bonded solvents should possess sin structures (306].However,whereas water has been t oroughly studi d[17,176,307],th nner stru of oth solvents are still less well known [17 9.By way o example,the intermolec r 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 by strong dipole/dipole interactions 309 From the idea that the solvent only provides an indifferent 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 intramolecular reaction will be favoured over the undesired intermolecular reaction by high dilution with an inert solvent [18.310. The assumption of forces of interaction between solvent and solute led,on the other 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 suffices.When a chemical er.The strange pr was not a new and more stable form of pureics ertie high concentrations of siliceous material d

gaseous state, but instead move in the potential field of their neighbours. The potential energy of a liquid is higher than that of its solid by about 10%. Therefore, the heat of fusion 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 fine structure 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 describe the structure of water. However, all these models prove themselves untenable for a complete description of the physico-chemical properties of water and an interpretation of its anomalies [304]. Fig. 2-1 should make clear the complexity of the inner structure of water. Liquid water consists both of bound ordered regions of a regular lattice, and regions 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, and cages. There are chains and small polymers as well as bound, free, and trapped water molecules [9, 176]. The currently accepted view of the structure of liquid water treats it as a dynamic three-dimensional hydrogen-bonded network, without a significant num￾ber of non-bonded water molecules, that retains several of the structural characteristics of ice (i.e. tetrahedral molecular packing with each water molecule hydrogen-bonded to four nearest neighbours), although the strict tetrahedrality is lost [176]. Its dynamic behaviour resembles that of most other liquids, with short rotational and translational correlation times of the order of 0.1 to 10 ps, indicating high hydrogen-bond exchange rates [176, 305]. In principle, other hydrogen-bonded solvents should possess similar complicated structures [306]. However, whereas water has been thoroughly studied [17, 176, 307], the inner structures of other solvents are still less well known [172, 177–179]. By way of example, 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 by strong dipole/dipole interactions [309]. 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 intramolecular reaction will be favoured over the undesired intermolecular reaction by high dilution with an inert solvent [18, 310]. The assumption of forces of interaction between solvent and solute led, on the other 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 chemical * 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. 6 2 Solute-Solvent Interactions

2.1 Solutions 7 ree Wo rdere Chain wo-dimensional schematic diagram of the three-dimensional structure of lio

Fig. 2-1. Two-dimensional schematic diagram of the three-dimensional structure of liquid water [9]. 2.1 Solutions 7