Solvent effects

In

over a chemical reaction.

A

solute

dissolves in a solvent when solvent-solute interactions are more favorable than solute-solute interaction.

Effects on stability

Different solvents can affect the equilibrium constant of a reaction by differential stabilization of the reactant or product. The equilibrium is shifted in the direction of the substance that is preferentially stabilized. Stabilization of the reactant or product can occur through any of the different non-covalent interactions with the solvent such as H-bonding, dipole-dipole interactions, van der Waals interactions etc.

Acid-base equilibria

The ionization equilibrium of an acid or a base is affected by a solvent change. The effect of the solvent is not only because of its acidity or basicity but also because of its

and its ability to preferentially solvate and thus stabilize certain species in acid-base equilibria. A change in the solvating ability or dielectric constant can thus influence the acidity or basicity.

Solvent properties at 25 °C

Solvent	Dielectric constant[1]
Acetonitrile	37
Dimethylsulfoxide	47
Water	78

In the table above, it can be seen that water is the most polar-solvent, followed by DMSO, and then acetonitrile. Consider the following acid dissociation equilibrium:

HA ⇌ A⁻ + H⁺

Water, being the most polar-solvent listed above, stabilizes the ionized species to a greater extent than does DMSO or Acetonitrile. Ionization - and, thus, acidity - would be greatest in water and lesser in DMSO and Acetonitrile, as seen in the table below, which shows pK_a values at 25 °C for acetonitrile (ACN)^[2][3][4] and dimethyl sulfoxide (DMSO)^[5] and water.

pK_a values of acids

HA ⇌ A− + H+	ACN	DMSO	water
p-Toluenesulfonic acid	8.5	0.9	strong
2,4-Dinitrophenol	16.66	5.1	3.9
Benzoic acid	21.51	11.1	4.2
Acetic acid	23.51	12.6	4.756
Phenol	29.14	18.0	9.99

Keto–enol equilibria

Many

H-bonding with the solvent. As a result, solvents of low polarity that do not readily participate in H-bonding allow cis-enolic stabilization by intramolecular H-bonding.

Solvent	${\displaystyle {\mathbf {K} }_{\mathrm {T} }={\frac {[cis-enol]}{[diketo]}}}$
Gas phase	11.7
Cyclohexane	42
Tetrahydrofuran	7.2
Benzene	14.7
Ethanol	5.8
Dichloromethane	4.2
Water	0.23

Effects on reaction rates

Often, reactivity and reaction mechanisms are pictured as the behavior of isolated molecules in which the solvent is treated as a passive support. However, the nature of the solvent can actually influence reaction rates and order of a chemical reaction.^[6][7][8][9]

Performing a reaction without solvent can affect reaction-rate for reactions with

techniques where physical methods are used to control reactions rather than solvents are methods are methods for affecting reactions in the absence of solvent.

Equilibrium-solvent effects

Solvents can affect rates through equilibrium-solvent effects that can be explained on the basis of the transition state theory. In essence, the reaction rates are influenced by differential solvation of the starting material and transition state by the solvent. When the reactant molecules proceed to the transition state, the solvent molecules orient themselves to stabilize the transition state. If the transition state is stabilized to a greater extent than the starting material then the reaction proceeds faster. If the starting material is stabilized to a greater extent than the transition state then the reaction proceeds slower. However, such differential solvation requires rapid reorientational relaxation of the solvent (from the transition state orientation back to the ground-state orientation). Thus, equilibrium-solvent effects are observed in reactions that tend to have sharp barriers and weakly dipolar, rapidly relaxing solvents.^[6]

Frictional solvent effects

The equilibrium hypothesis does not stand for very rapid chemical reactions in which the transition state theory breaks down. In such cases involving strongly dipolar, slowly relaxing solvents, solvation of the transition state does not play a very large role in affecting the reaction rate. Instead, dynamic contributions of the solvent (such as friction, density, internal pressure, or viscosity) play a large role in affecting the reaction rate.^[6][9]

Hughes–Ingold rules

The effect of solvent on elimination and nucleophillic substitution reactions was originally studied by British chemists

Hughes and Ingold then made certain assumptions about the extent of solvation to be expected in these situations:

• increasing magnitude of charge will increase solvation
• increasing delocalization will decrease solvation
• loss of charge will decrease solvation more than the dispersal of charge [6]

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
• 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 on the rates of reaction when there is little or no difference in charge between the reactants and the activated complex.^[6]

Reaction examples

Substitution reactions

The solvent used in

As such, solvent conditions significantly affect the performance of a reaction with certain solvent conditions favoring one reaction mechanism over another. For S_N1 reactions the solvent's ability to stabilize the intermediate carbocation is of direct importance to its viability as a suitable solvent. The ability of polar solvents to increase the rate of S_N1 reactions is a result of the polar solvent's solvating the reactant intermediate species, i.e., the carbocation, thereby decreasing the intermediate energy relative to the starting material. The following table shows the relative solvolysis rates of tert-butyl chloride with acetic acid (CH₃CO₂H), methanol (CH₃OH), and water (H₂O).

Solvent	Dielectric Constant, ε	Relative Rate
CH3CO2H	6	1
CH3OH	33	4
H2O	78	150,000

The case for

however, for demonstration of principle for solvent polarity on S_N2 reaction rates, steric effects may be neglected.

Solvent	Dielectric Constant, ε	Relative Rate	Type
CH3OH	33	1	Protic
H2O	78	7	Protic
DMSO	49	1,300	Aprotic
DMF	37	2800	Aprotic
CH3CN	38	5000	Aprotic

A comparison of S_N1 to S_N2 reactions is to the right. On the left is an S_N1 reaction coordinate diagram. Note the decrease in ΔG^‡_activation for the polar-solvent reaction conditions. This arises from the fact that polar solvents stabilize the formation of the carbocation intermediate to a greater extent than the non-polar-solvent conditions. This is apparent in the ΔE_a, ΔΔG^‡_activation. On the right is an S_N2 reaction coordinate diagram. Note the decreased ΔG^‡_activation for the non-polar-solvent reaction conditions. Polar solvents stabilize the reactants to a greater extent than the non-polar-solvent conditions by solvating the negative charge on the nucleophile, making it less available to react with the electrophile.

Transition-metal-catalyzed reactions

The reactions involving charged transition metal complexes (cationic or anionic) are dramatically influenced by solvation, especially in the polar media. As high as 30-50 kcal/mol changes in the potential energy surface (activation energies and relative stability) were calculated if the charge of the metal species was changed during the chemical transformation.^[13]

Free radical syntheses

Many free radical-based syntheses show large kinetic solvent effects that can reduce the rate of reaction and cause a planned reaction to follow an unwanted pathway.^[14]

See also

• Cage effect

References