Menschutkin reaction, solvent

Figure 8-3. Plot of free energy of activation for the Menschutkin reaction EtjN + EtI Et4N + 1 against the Kirkwood dielectric constant function. Data are from Table 8-5, where the solvents are identified.

Table 8-10. Solvent Effects and Transfer Free Energies for the Menschutkin Reaction of Triethylamine and Ethyl Iodide" ...

Figure 8-6. Ploi according to Fig. 8-5 of transfer free energies of the transition state (ordinate) and reactant state (abscissa) for the Menschutkin reaction of triethylamine and ethyl iodide. The reference solvent is N, Af-dimethylformamide (No. 27). Data are from Table 8-10, where the solvents are identified by number. Closed circles are polychlorinated solvents.

The Menschutkin reaction was carried out as a test reaction to show the feasibility of such novel micro flow concepts that allow to process fouling-sensitive reactions (see also Section 4.2.6 here another test reaction is decribed for the same purpose) [78]. The reaction of alkyl bromide with ternary bases such as pyridine or triethylamine gives quaternary salts insoluble in most solvents. Often, fairly rapid precipitation of this salt occurs, hence ideally serving as a test reaction for fouling sensitivity of micro-channel devices. The reaction of 4,4 -bipyridyl and ethyl bromoacetate [78] belongs to the category of fast-predpitating Menschutkin reactions, as the halide function is activated by the carbonyl fimction. 

To pursue the development of environmentally benign synthesis routes for ionic liquids, the alkylation step (Menschutkin reaction) was investigated by the authors in detail. The preparation of the ionic liquid 1-hexyl-3-methyhmidazohum chloride ([CeMlMJCl) was taken as a representative experiment (Scheme 7.2). The process parameters temperature (T = 70-100°C), solvent (ethanol, xylene, cyclohexane, n-heptane, solvent free), concentration of the N-base (c = 1.6-6.7 M), molar ratio n n = 1 0.5-1 4) and reaction time (f = 10-144 h) were investigated. In addition, the N-base was altered in order to proof the transferability of the reaction parameters. 

In this contribution, we describe and illustrate the latest generalizations and developments[1]-[3] of a theory of recent formulation[4]-[6] for the study of chemical reactions in solution. This theory combines the powerful interpretive framework of Valence Bond (VB) theory [7] — so well known to chemists — with a dielectric continuum description of the solvent. The latter includes the quantization of the solvent electronic polarization[5, 6] and also accounts for nonequilibrium solvation effects. Compared to earlier, related efforts[4]-[6], [8]-[10], the theory [l]-[3] includes the boundary conditions on the solute cavity in a fashion related to that of Tomasi[ll] for equilibrium problems, and can be applied to reaction systems which require more than two VB states for their description, namely bimolecular Sjy2 reactions ],[8](b),[12],[13] X + RY XR + Y, acid ionizations[8](a),[14] HA +B —> A + HB+, and Menschutkin reactions[7](b), among other reactions. Compared to the various reaction field theories in use[ll],[15]-[21] (some of which are discussed in the present volume), the theory is distinguished by its quantization of the solvent electronic polarization (which in general leads to deviations from a Self-consistent limiting behavior), the inclusion of nonequilibrium solvation — so important for chemical reactions, and the VB perspective. Further historical perspective and discussion of connections to other work may be found in Ref.[l],... 

Information as to the nature of the transition state in reaction (71) may be obtained through a comparison of AG f(Tr) values with those for other transition states and those for various model solutes. Data are available62 on solvent effects on the transition state in the Menschutkin reaction... 

Fig. 10.2. Predictions of the logarithmic relative rate constants of the Menschutkin reaction in various solvents [C32]. The COSMO polarization charge densities a of the transition state are visualized in the inset.

Solvent effect on rate constants. In this section, the rate constant will be predicted qualitatively in CO2 for the Diels-Alder cycloaddition of isoprene and maleic anhydride, a reaction which has been well-characterized in the liquid state (23,24). In a previous paper, we used E data for phenol blue in ethylene to predict the rate constant of the Menschutkin reaction of tripropylamine and methyliodide (19). The reaction mechanisms are quite different, yet the solvent effect on the rate constant of both reactions can be correlated with E of phenol blue in liquid solvents. The dipole moment increases in the Menschutkin reaction going from the reactant state to the transition state and in phenol blue during electronic excitation, so that the two phenomena are correlated. In the above Diels-Alder reaction, the reaction coordinate is isopolar with a negative activation volume (8,23),... 

There is no need for the transition states to be charged for these effects to be observed. As noted in Section 2, dipolar aprotic solvents also interact strongly with polarizable neutral species. The data for Menschutkin reactions on transfer from methanol to DMF (Table 12 ... 

An example of reaction type (c) in Table 5-4 is the well-known Menschutkin reaction [30] between tertiary amines and primary haloalkanes yielding quaternary ammonium salts. Its solvent dependence was studied very thoroughly by a number of investigators [51-65, 491-496, 786-789]. For instance, the reaction of tri-n-propylamine with iodomethane at 20 °C is 120 times faster in diethyl ether, 13000 times faster in chloroform, and 110000 times faster in nitromethane than in -hexane [60]. It has been estimated that the activated complex of this Menschutkin reaction should have a dipole moment of ca. 29 10 Cm (8.7 D) [23, 64], which is much larger than the dipole moments of the reactant molecules (tris- -propylamine 2.3 10 Cm = 0.70 D iodomethane 5.5 10-3 1 64 D) [64]. 

Table 5-5. Absolute and relative rate constants, Gibbs activation energies, activation enthalpies, and activation entropies of the Menschutkin reaction between triethylamine and iodoethane in twelve solvents at 50 °C [59],...

For many physical organic chemists, the Menschutkin reaction was a kind of guinea pig , which has been extensively used for the study of solvent effects on chemical reactivity. A comprehensive review of this reaction has been given by Abboud el al. [786], More recent theoretical treatments of the solvent influence on Menschutkin reactions can be found in references [787-789]. 

Glasstone, Laidler, and Eyring [2] were the first to correlate rate data for some Menschutkin reactions according to Eq. (5-87), and they found, in particular, that a linear correlation between g k/ko) and (sr — l)/(2er + 1) is observed in the binary solvent mixture benzene/alcohol, while in benzene/nitrobenzene a monotonous deviation from the linear dependence is observed. 

Fig. 5-10. Correlation between lg(k/ko) [56] and the Kirkwood function (cr — l)/(2 r + 1) for the Menschutkin reaction between triethylamine and iodoethane at 40 °C in binary acetone/benzene and acetone/l,4-dioxane mixtures (rate constants relative to acetone as common standard solvent).

If one compares the rate constants for the same Menschutkin reaction with Kirkwood s parameter in thirty-two pure aprotic and dipolar non-HBD solvents [59, 64], one still finds a rough correlation, but the points are widely scattered as shown in Fig. 5-11. 

Extending the media used for the Menschutkin reaction to protic solvents such as alcohols leads to an even worse correlation, as shown in Fig. 5-12 for the quaternization of l,4-diazabicyclo[2.2.2]octane with (2-bromoethyl)benzene studied in a total of thirty-six solvents [65], The group of protic solvents is separated from the assembly of non-HBD solvents, each group showing a very rough but distinct correlation with the function of relative permittivity. Such behaviour has also been observed for several other Menschutkin reactions [60, 61],... 

Although Eq. (5-87) is often qualitatively obeyed, as has been frequently mentioned, there is no exact linear correlation between the rate of Menschutkin reactions and the functions of relative permittivity as in the case of Fig. 5-12 [246, 247]. A complete absence of a regular effect of changes in the dielectric properties of the solvent on the reaction rate has also been observed [248, 249]. Sometimes a satisfactory correlation has been obtained because the reaction under consideration was studied in only a limited... 

As the data for the Menschutkin reactions indicate, the character of the solute-solvent interactions is more complex than described by Eq. (5-87). It is evident that functions of relative permittivity alone, as given in Eq. (5-87), are not useful for describing the solvent effect on reactions between dipolar reactants, except in certain special cases, such as when a mixture of two solvents is used. In addition to electrostatic forces, non-electrostatic interactions, such as dispersion forces and hydrogen-bonding, must also be involved in Menschutkin reactions. 

As seen from Fig. 5-11, although the three halobenzenes (points nos. 8, 10, and 11) have similar values of fir, when used as solvents they lead to different reaction rates, lodobenzene (no. 8), with the lowest value, gives the largest rate. This observation strongly suggests that the polarizability of the solvent is an important factor in stabilizing the dipolar activated complex of this reaction. This was confirmed by Reinheimer el al. [57], who studied some Menschutkin reactions in benzene and its chloro, bromo, and iodo derivatives. They showed that the rate of the reaction increases with increasing polarizability of the solvent. 

Similar results are found for the above-mentioned Menschutkin reaction (c). The added pro tic solvent can also combine with the main solvent. Such solvent/solvent association leads to a diminution of the specific inhibitory and catalytic effect of protic solvents on the Sn2 reaction (c) [584], The basicity of the main solvent determines the extent of deactivation of the protic solvent through H-bond association this is analogous to Eq. (5-107). 

Contrary to reactions going through isopolar transition states, reactions of types 3 to 8 in Table 5-25, which involve formation, dispersal or destruction of charge, should exhibit large solvent effects on their activation volumes. This is shown in Table 5-27 for the Sn2 substitution reaction between triethylamine and iodoethane [441], an example of the well-known Menschutkin reaction, the pressure dependence of which has been investigated thoroughly [439-445, 755],... 

Table 5-27. Effect of external pressure and solvent polarity on reaction rate and activation volume of the Menschutkin reaction between triethylamine and iodoethane at 50 °C [441] cf. also Table 5-5 in Section 5.3.1 [59].

In addition to the application of SnI reactions as model reactions for the evaluation of solvent polarity, Drougard and Decroocq [48] suggested that the value of Ig kj for the Sn2 Menschutkin reaction of tri-n-propylamine and iodomethane at 20 °C -termed according to Eq. (7-21) - should also be used as a general measure of solvent polarity. 

Z values have been widely used to correlate other solvent-sensitive processes with solvent polarity, e.g. the a absorption of haloalkanes [61], the n n and n n absorption of 4-methyl-3-penten-2-one [62], the n n absorption of phenol blue [62], the CT absorption of tropylium iodide [63], as well as many kinetic data (Menschutkin reactions, Finkelstein reactions, etc. [62]). Copol5mierized pyridinium iodides, embedded in the polymer chain, have also been used as solvatochromic reporter molecules for the determination of microenvironment polarities in synthetic polymers [173]. No correlation was observed between Z values and the relative permittivity e, or functions thereof [317]. Measurement of solvent polarities using empirical parameters such as Z values has already found favour in textbooks for practical courses in physical organic chemistry [64]. 

Fig. 7-6 demonstrates the correlation between itT(30) and the relative rates for the Sn2 Menschutkin reaction between a tertiary amine and a haloalkane in non-HBD solvents. The values of the second-order rate constants are taken from the compilation made by Abraham and Grellier [110]. 

---