SOLVENT

1. holds together efficiently reagents that require collisional activation breaks the bond of the crystal lattice by dissolution • activity interacts with the solute by changing its condensed phase that possess a certain mobility • free energy • reactivity SOLVENT EFFECTS SOLVENT Many reactions take place with difficulty in gas phase and when performed in solution their rate can be strongly depending on the solvent: the main example is the proton transfert reaction.

2. When solvent effects reach this magnitude, solvent cannot be ignored and must be considered as a true catalyst of the reaction.

3. SOLVENTS • low dipole moment • no formation of hydrogen bonds • high dipole moment • formation of hydrogen bonds • NON POLAR APROTIC • does not contain acid groups • interaction through weak forces • PROTIC • contain an acid group that can give a proton - hydrocarbons, also halogenated - ethers -OH, -NH ROH, RNH2, RCOOH, H2O • DIPOLAR APROTIC • do not contain acid groups

4. SOLVENT EFFECTS for example DIELECTRIC CONSTANT (the ability of the solvent to increase the capacitance of a capacitor) macroscopic aspects microscopic aspects depends on depends on the bulk of the solvent permanent dipole polarizability (the ease of distortion of the electronic cloud)

5. The answer that a solvent gives in the charge distribution when the reaction takes place, is an important feature of solvent molecules. • The dielectric constant is a good indicator of the ability of a solvent to arrange charge separation. • Anyway it is not the unique factor because it is a macroscopic feature and it gives little information about short range interactions of solvent molecules with solute, that depends on the specific structure of the molecule.

6. Solvation reduces free energy of solute molecules in equilibrium and influences the value of the free energy of the reaction. Consequently it influences the equilibrium constant. • For example, 2-pyridone is in equilibrium with 2-hydroxy pyridine and the more the solvent is polar the more the equilibrium is shifted to the right. • Although 2-hydroxypyridine is more stable because of the aromaticity of the ring, solvation can invert the situation. • Both tautomers can give hydrogen bonds, but 2-pyridone is more stabilized by solvation, owing to its higher dipole moment.

7. The effect of solvent on elimination and nucleophilic substitution reactions was originally studied by Hughes and Ingold. • Using a simple solvation model which only considered pure electrostatic interactions between ions or dipolar molecules and solvents in initial and transition states, all nucleophilic and elimination reactions were organized into different charge types (neutral, positively or negatively charged). The applicable effect of these general assumptions are shown in the following examples: • An increase in solvent polarity accelerates the rates of reactions where a charge is developed in the activated complex from neutral or slightly charged reactant

8. An increase in solvent polarity decreases the rates of reactions where there is less charge in the activated complex in comparison to the starting materials • A change in solvent polarity will have little or no effect of the rates of reaction when there is little or no difference in charge between the reactants and the activated complex.

9. The variation of the reaction rate with solvent properties furnishes informations about the mechanism. • Measuring the reaction rate in a serie of solvents of different polarity, a qualitative information about the influence of the solvent on the reaction rate can be obtained. • Sometimes it can be sufficient to make mesurements only in two solvents of very different polarity, such as cyclohexane (extremely nonpolar) and acetonitrile (polar aprotic) to accept or discard a certain mechanism, as it can be seen from the following examples.

10. The effect of the solvent on the reaction between maleic anhydride and 2-methylbutadiene is very poor. It indicates that the transition state is not particularly stabilized by solvation, with respect to the reagents. This experimental evidence allows to discard the hypothesis of a transition state with charge separation with respect to other two ipotheses of radical formation or concerted reaction.

11. On the other hand the reaction between vinylether and tetracyanoethylene shows a very strong solvent effect (kacetonitrile/kcyclohexane = 10800) and this experimental evidence allows the hypothesis of a transition state with high charge separation.

12. In the last example the cycloaddition of the same vinylether to diphenylketene shows a low solvent effect (kacetonitrile/kcyclohexane = 163) and this fact can be explained as a dipolar cycloaddition as but also as a more polarized transition state, very “early”, with poor charge separation, similar to the one shown in the previous reaction.

13. Same reactions may be favoured by a non-polar solvent more than a polar one: this pyramidal allylsulfoxide racemizes passing through a transition state with a dipole moment lower than the one of the allyl sulfoxide itself. • A simple inversion does not explain this change in the dipole moment, and the hypothesis is that the reaction proceeds through the sulphenyl ester, with allylic rearrangement.

14. A solvent can influence the rate of two competitive reactions in a different way and consequently to change the solvent can modify very much the composition of a mixture of products, if it comes from reaction pathways of competitive reactions. • An important example is the increased nucleophilicity of many anions in polar aprotic solvents with respect to the protic ones. • In protic solvents anions are strongly solvated by hydrogen bonds, particularly the ones with high charge concetration on oxygen or nitrogen atoms. • Such hydrogen bonds decrease the nucleophilic character of the anion.

15. In aprotic solvents there are not protons available for hydrogen bond, so the electrons of the anion are more available for the reaction. In other words, the anion is less stable because it lacks solvation stabilization. • Ions are not soluble in apolar solvents. Metal cations as Na+ or K+ are strongly solvated by polar aprotic solvents as dimethylformamide or dimethyl sulfoxide, in which oxygen atom releases electrons towards the cation. • Dissolved salts are dissociated and the corresponding anions are strongly reactive, because unsolvated and separed from cations.

16. Solvent effects may modify both the energies of the reagent and of the transition state. The difference between the two solvation effects is at the basis of the change in activation energy and in reaction rate. • For example the hydrolysis of esters with OH- • This reaction is more rapid in DMSO/H2O than in EtOH/H2O. It is possible to evaluate the reagents solvation with respect to the transition state with measurements of the heat of reaction of the reagents in each solvent.

17. Transition state 10.0 kcal/mol Transition state DH‡ = 10.9 kcal/mol DMSO/H2O DH‡ = 14.9 kcal/mol DH of reagents displacement 14.0 kcal/mol EtOH/H2O • Both reagents and transition state are more solvated in ethanol/water. The increase in the reaction rate arises from the major solvation of the hydroxide ion, smaller than the big anions involved in the transition state. • Generally the solvation forces are stronger for hard and small cations, and diminishes with dimensions and soft character.