The effect of solvents on reaction rates

In nucleophilic substitutions, we must first know whether the substitution is Sj,[2 or Sjsjl. Table 1.11.1, according to Ingold et a/., shows the possible reaction types and the relevant solvent effects. 

Influence of solvent polarity increase on the reaction rate 

The effect of polar aprotic solvents on reaction rates should be also commented. These are solvents without hydroxyl groups, but with a relatively high dipole moment and rather high relative permittivity (dielectric constant). Such solvents are, e.g., acetone, acetonitrile, dimethylformamide (DMF), dimethyl sulfoxide, (DMSO), hexamethylphosphoric triamide (HMPT). 

Many replacement reactions are often much faster in polar aprotic solvents than in hydroxylic solvents. Thus, the reaction of methyl bromide with iodide is about 500 times faster in acetone than in methyl alcohol. In addition, methyl iodide reacts with chloride about a million times faster in DMF than in methyl alcohol. This happens because the OH group of hydroxylic solvents solvates anions, forming the hydrogen bond (ROH- X -HOR). The solvated anions are therefore much less reactive. On the other hand, aprotic solvents having no hydrogen are unable to form hydrogen bonds. Anions in polar aprotic solvents are therefore more free, more reactive, and thus better nucleophiles. Another example of a strong solvent effect on a 8 2 reaction is the bimolecular replacement of bromide by azide in 1-bromobutane  

If the relative rate in methanol is taken as 1, then the rates in water, DMSO, DMF, and methyl cyanide (acetonitrile) are 7, 1300, 2800, and 5000, respectively. It is quite clear that the entering azide nucleophile is best solvated in methanol and least solvated in acetonitrile. Thus, the largest amount of energy is required to free azide from methanol in order to form the transition state, and the least energy is needed to remove the acetonitrile solvent. 

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This effect has been studied quite intensively in recent years in order to understand better the course and nature of electrode reactions. In particular, simple charge-transfer reactions have been used as models to check predictions of modern theories of the effect of solvents on reaction rates. 

The combination of a good catalyst with a preferred solvent for the desired organic reaction can benefit the reaction system. Several solvents were used to study the effects of solvent on reaction rates and product selectivity on the newly-developed low palladium content catalyst. For N-phenylbenzylamine debenzylation, higher hydrogenation activity was obtained by employing methanol as a solvent. THF (tetrahydrofuran), and cyclohexane were found to be less effective. Studer and Blaser [7] studied the solvent effects on catalytic debenzylation of 4-chloro-N,N-dibenzyl anihne and foimd that the overall reaction rate was slower with the use of non-polar solvents. 

Solvent polarity dramatically affects the reaction rate. To predict the effect of solvents on reaction rates, the polarity of the reactants is compared with that of the transition state. If the transition state is more polar than the reactants, the transition state will be more stabilized than the reactants in a polar solvent. This will decrease AG, resulting in a faster reaction. On the other hand, if the reactants are more polar than the transition state, increasing solvent polarity will stabilize reactants more, resulting in an increase in AG and a decrease in the reaction rate. In general, rates of Sn1 reactions are faster in polar solvents while those of 8 2 reactions involving negative nucleophiles are faster in aprotic solvents. 

Reichardt, C. (2003). Solvents and Solvent Effects in Organic Chemistry, 3rd ed., Wdey- VCH Publishers, New York. A standard reference work on the effects of solvent on reaction rates. Highly recommended. 

Many articles are pubHshed that have the effect of solvent on reaction rate as a significant component of the work. This is particularly true of the study of reactions in organic chemistry. After examining several journals, select an article in which the role of the solvent is discussed from the standpoint of kinetics. Make sure that enough data are presented to enable you to perform the following analysis. 

If a simple electrostatic model (neglecting ionic-strength effects) is considered, the effect of solvent on reaction rates of polar molecules can be assessed by calculating the free energy of solvation of a spherical molecule of radius r containing a point dipole of magnitude fii at its center. The value obtained by Kirkwood [4] with a reference state of c = 1 (all other state variables being held constant) is... 

The basic principles underlying the effects of solvent on reaction rate -solvation of reactants and transition states - are reasonably well understood and can be used in a predictive sense to aid in the selection of the optimum solvent for a particular transformation. 

The effects of solvents on reaction rates have been studied most extensively on unimolecular solvolysis reactions (S l) and on bimolecular nucleophilic substitution reactions (Sj 2). Absolute rate theory specifies that the activated complex in the transition state is at equilibrium with the reactants and is formed on provision of the activation (Gibbs) energy, AG. In other words, the energy barrier that the reaction must pass to proceed has to be overcome. The specific rate constant is given by ... 

More than a century ago, Menschutkin [7] noted that a reaction in solution cannot be separated from the medium in which it occurs. In fact, the effects of solvent on reaction rates can be dramatic. In the reactions studied by Menschutkin, such as... 

Generally speaking, the influence of solvent on reaction rates (equilibria) is determined by the difference between the effects < n the stability of transition states (products) and reactants. According to what Leffler and Grunwald (1963) call the first approximation, the free energy of a solute molecule RX is given by the sum of internal and solvent contributions, as shown in (59). The... 

The effect of dilution on reaction rate can be studied by distilling more solvent into E. The reaction can be stopped by breaking the seal of Fwith G and cooling E to distil the killing agent into the reaction mixture. 

The reactions of [Co(CN)s(H20)]2 with Nf6768 and SCN-68 have been reinvestigated and important differences found which indicate that the evidence in favour of limiting kinetics is not as clear as originally supposed. In particular, deviations from the simple second-order rate law for anation, rate = /c[Co(CN)5(H20)2 ][Y ], appear to be small and the question of reaction mechanism remains somewhat open at present. The effect of solvent on reaction between [Co(CN)5-(H20)]2 and N 69 and the small positive activation volumes for anation by Br-, I- and SCN-70 are indicative of a dissociative mechanism, but the existence of a long-lived five-coordinate intermediate has not been definitively established. 

Reactions of Cobalt(ll) with Peroxy Radicals and the Effect of Solvent on Oxidation Rate... 

Another factor to be considered in the use of SC-CO2 as a reaction solvent deals with the possible effect of pressure on reaction rate (and selectivity) (9). For the hypothetical reaction A + B -> C, the effect of pressure on reaction rate is expressed by equation 3, where k is the rate constant for the reaction and AV (the volume of activation) is the difference in molar volume between the transition state and reactants (AV - Vg) (10). Reactions exhibiting negative volumes of... 

They confirmed that the reactions in ionic liquids conformed to the Hughes-Ingold mles for the prediction of the effects of solvents on reactions, with the ionic liquids being regarded as polar solvents. The LSER approach allowed them to determine that the rates of the reactions depended upon both generalized... 

Addition of a water immiscible solvent will decrease the reaction rate because it will decrease the partition of the reactant into the aqueous phase. In order to be able to predict the effect of agitation on reaction rate it is necessary to understand what other factors, in addition to solubility, control the reaction rate. Depending on the reaction rate reaction may occur in the bulk aqueous phase or in the diffusion film adjacent to the interface. 

The first systematic investigation on the influence of solvent on reaction rates was reported by Menschutkin(l) as long ago as 1890. Quite soon after this study, chemists began to consider whether or not solvent influences on reaction rates were connected with the effect of solvents on the reactants (i.e. with initial-state effects). However, a careful and extensive investigation by Von Halban(2) in 1913 showed conclusively that for the reaction of trimethylamine with p-nitrobenzyl chloride, solvent effects on the reactants could not account quantitatively for the overall influence of solvent on the reaction rate constant. Little further progress was made on these lines until the advent of transition state theory, when it then became clear that in principle it was possible to dissect the influence of solvent on rate constants into initial-state and transition-state contributions(3-5). 

The effect of solvent on the rate, E, and dS can be derived from the data on haloquinolines and their A-oxides (Tables X and XI), on halonitronaphthalenes (Tables XII and XIII), and on halodinitro-naphthalenes (Table XVI). Depending on the nature of the reaction, the relative reactivity of two compounds can be substantially different in different solvents. For example, piperidination of 2-chloroquinoline (Table X, lines 3 and 4) compared to 2-chloroquinoxaline (Table XV,... 

Reactions of Phosphonium Salts.- Interest continues in the effects of solvent on the rate of alkaline decomposition of phosphonium salts. It has now been shown that, in the respective reactions of hydroxide ion and methoxide ion with tetraphenyl-phosphonium bromide in mixtures of DMSO and methanol, the rates of the reactions increase as the proportion of the dipolar aprotic... 

Lowering the temperature of the reaction would certainly decrease the rate of acetal hydrolysis and thereby partially remove one of the causes of overoxidation. This would simultaneously decrease the rate of oxidation by periodate. Although no comprehensive study of the effect of temperature on oxidation rates has been made, the number of reactions successfully dealt with in the temperature range of 0 to 6°31 39 78 113 126 130 i33, i64, us, 203,210,266,267 indicates that lowered temperatures do not affect the rates unfavorably. In order to obtain the maximum of selective oxidation and the minimum of overoxidation, periodate oxidations should be performed at as low a temperature as is practicable in relation to the solvent system used and the solubility of the reactants therein. 

The effect of solvents on the kinetics of addition to hexyne-1 was studied (56) with Et3SiH. Solvents with dielectric constants from 1.6 to 20.7 had scarcely any measureable effects on the rates of addition. Electron-donating solvents such as pyridine or dimethyl sulfoxide even in very small amounts stopped the reaction entirely. 

The experiments show that the dilution of all the monomers leads to a change of rate, and I contend that at the earliest stage of dilution the polymerizations are still mainly unimolecular and I offer an explanation for the effects of solvents on the rate of the unimolecular reactions. Since the rate constants, k, are defined by (4.1) and (4.14) they can only be calculated if [P+ M] is known. As explained in Section 3b, there are reasons for believing that for cyclopentadiene and for isobutene [P+ M = c, but for the former there are no results for solutions, and for the latter no c values are available, so that for these monomers could only be calculated for the bulk polymerizations. 

However, before the kinetics we need to discuss one more electrochemical matter, namely how the dielectric constant D of the whole reaction mixture affects the rate-constants kpl+, kp and. Because of the irregular shape of the cations, it is unlikely that this influence will obey the appropriate Laidler equations (k varies as 1/D). For the the appropriate equation would be that for a dipole-dipole reaction, which predicts an increase of the rate-constant with increasing D. The effect of solvents on the kpl+ is discussed by Plesch (1993). 

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