Reaction-solvent indices

Comparison of reaction rates k in a solvent S and k in a reference solvent (index o) yields... 

ILs are able to dissolve some nonpolar molecnles as well as some very polar ones. They have negligible vapor pressnre and excellent thermal stabilities, can act as green solvents, and replace volatile organic solvents in several chemical reactions. Their physicochemical properties [12] can be modified by changing the cation, anion, or substituent (R-gronps) hence, ILs can be nsed not only as reaction solvents but also as catalysts or catalytic solvents. ILs have also been referred to as designer solvents [13] as their physical and chemical properties snch as solubility, density, refractive index, and viscosity can be adjnsted by a careful choice of cation, anion, or both [14-16]. 

The solvent index is arranged according to single solvents, nonaqueous-aqueous mixtures and nonaqueous-nonaqueous mixtm-es. Individual solvent systems are indexed accordii to solubilities, pKsp, emf, potentiometric titrations, vapor pressure, cryoscopy, heats of solution, polarography, ligand exchange rates, electrode reactions, electrical double layer, spectroscopy, and organic electrolyte batteries. 

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

The susceptibility or mixing coefficients, pj and pj , depend upon the position of the substituent (indicated by the index, /) with respect to the reaction (or detector) center, the nature of the measurement at this center, and the conditions of solvent and temperature. It has been held that the p/scale of polar effects has wide general applicability (4), holding for substituents bonded to an sp or sp carbon atom (5) and, perhaps, to other elements (6). The or scale, however, has been thought to be more narrowly defined (7), holding with precision only for systems of analogous pi electronic frameworks (i.e., having a dependence on reaction type and conditions, as well as on position of substitution). 

Only a little effort is necessary to reduce solvent 1 demand used during reaction scale-up. The quantity used in the laboratory stage was reduced to 59% in the operation stage (Table 5.1). However, related to substrate 2, 96% of solvent 1 is still used. Thus, 87% of the original quantity of solvent will be fed to the incinerator for disposal, while the recycle rate is only 9.1% (from 96% to 87%, Table 5.1). Considering that there is a factor of five difference in solvent 1 demand between the operation scale and the literature procedure (see the segments Solvent of the mass index, in Figure 5.10), the potential for optimiz-... 

In contrast to the quantity of solvent 1 used during the reaction, the quantity of extraction solvent 2 (work up) increases during scale up (Laboratory 100% Operation 103%), especially when it is related to substrate 2 (Laboratory 100% Operation 169%). Compared to the yield obtained from the literature protocol in which an extraction procedure is missing, an efficient extraction seems to be important in order to achieve sufficient product accumulation. However, as the mass index and the environmental factor demonstrate with respect to the possibility for reducing the volume of water used (see above), solvent 2 demand should be able to be reduced as well, since less water use means less solvent is required for extraction. StiU, at least the recycle rate of solvent 2 is as high as 72.8% (from 169% to 46%, Table 5.1), regarding the current data of the technical operation scale. 

Figure 4 Dynamic dilution of sample for HPLC analysis of amidation/cyclization reaction. Transfer solvent methoxyethanol flow rate 1 ml/min. Detection refractive index.

The relationship between the geometry of the saddle point of index one (SPi-1) and the accessibility to the quantum transition states cannot be proved, but it can be postulated [43,172], To some extent, invariance of the geometry associated with the SPi-1 would entail an invariance of the quantum states responsible for the interconversion. Thus, if a chemical process follows the same mechanism in different solvents, the invariance of the geometry of the SPi-1 to solvent effects would ensure the mechanistic invariance. This idea has been proposed by us based on computational evidence during the study of some enzyme catalyzed reactions [94, 96, 97, 100-102, 173, 174, 181-184],... 

A theoretical study at a HF/3-21G level of stationary structures in view of modeling the kinetic and thermodynamic controls by solvent effects was carried out by Andres and coworkers [294], The reaction mechanism for the addition of azide anion to methyl 2,3-dideaoxy-2,3-epimino-oeL-eiythrofuranoside, methyl 2,3-anhydro-a-L-ciythrofuranoside and methyl 2,3-anhydro-P-L-eiythrofuranoside were investigated. The reaction mechanism presents alternative pathways (with two saddle points of index 1) which act in a kinetically competitive way. The results indicate that the inclusion of solvent effects changes the order of stability of products and saddle points. From the structural point of view, the solvent affects the energy of the saddles but not their geometric parameters. Other stationary points geometries are also stable. 

The most important route to 1-acylaminoanthraquinones involves reaction of 1-aminoanthraquinone with acid chlorides in an organic solvent. Reaction of 1-aminoanthraquinone with benzoylchloride in nitrobenzene at 100 to 150°C affords 1-benzoylaminoanthraquinone, a yellow pigment which is registered as Colour Index Constitution No. 60515. The reaction may also be performed in the presence of a tertiary amine, which acts as a proton acceptor ... 

In all cases the dielectric constant used is that of the pure solvent. Neglect of the solute is usually justified by its low concentration and the assumption that any necessary correction would be additive. In at least a few cases where the first two expressions have been employed the linearity of the results is to some extent dependent on how closely the refractive index of the solute meets the conditions n2 = 2.0 or 2.5 a situation not always recognized by the investigators. In one instance attempts have been made to clarify the role of solvent reaction field by examining solutes with different dipole moment orientations relative to the bonds involving coupled atoms. 

Ihrig and Smith extended their study by running a regression analysis including reaction field terms, dispersion terms and various combinations of the solvent refractive index and dielectric constant. The best least squares fit between VF F and solvent parameters was found with a linear function of the reaction field term and the dispersion term. The reaction field term was found to be approximately three times as important as the dispersion term and the coefficients of the terms were opposite in sign. 

These expressions appear more applieable to nonpolar solvents or mixtures than to polar solvents. The nature of the solvation process (and the radii and so forth of the solvated reactants) may stay approximately constant in the first situation but almost certainly will not in the seeond. The function (E>op A ) features in the reorganisation term Xq which is used for estimating rate constants for redox reactions (Eqn. 5.23). is the optical dielectric constant and Dj the static dielectric constant (= refractive index ). 

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