Rates constants with methyl iodide

Nucleophilic reactivity of the sulfur atom has received most attention. When neutral or very acidic medium is used, the nucleophilic reactivity occurs through the exocyclic sulfur atom. Kinetic studies (110) measure this nucleophilicity- towards methyl iodide for various 3-methyl-A-4-thiazoline-2-thiones. Rate constants are 200 times greater for these compounds than for the isomeric 2-(methylthio)thiazole. Thus 3-(2-pyridyl)-A-4-thiazoline-2-thione reacts at sulfur with methyl iodide (111). Methyl substitution on the ring doubles the rate constant. This high reactivity at sulfur means that, even when an amino (112, 113) or imino group (114) occupies the 5-position of the ring, alkylation takes place on sulfiu. For the same reason, 2-acetonyi derivatives are sometimes observed as by-products in the heterocyclization reaction of dithiocarba-mates with a-haloketones (115, 116). 

If the rate constants for quaternization of 2-alkylthiazoles depended on electronic factors, they would all be greater than that of thiazole, which has the low est pK. and all of the same order. The decrease in rate constants that is observed is attributed wholly to steric effects. In Table III-50 we report the main parameters for the reaction of 2-alkylthiazoles with methyl iodide. 

TABLE m-50. RATE CONSTANTS AND ACTD ATION PARAMETERS FOR THE REACTION OF 2-ALKYLTHl AZOLES WITH METHYL IODIDE IN NITROBENZENE (256)... 

TABLE rri-53. RATE CONSTANTS (fc x 10 ) FOR THE OUATERNIZATION OF 2-ALKYL AND 2,4-DIALKYLTHIA20LES WITH METHYL IODIDE IN NITROBENZENE AT 25°C (256)... 

TABLE ra-54. RATE AND ACTIVATION CONSTANTS FOR THE REACTION OF 5-ALKYLTHlAZOLES WITH METHYL IODIDE IN NITROBENZENE. (254). 

We have also correlated rate constants for the reaction of 3- or 4-substituted N,N-dimethylanilines with methyl iodide, 3- or 4-substituted benzoic acids with diphenyldia-zomethane and 3- or 4-substituted benzoyl chlorides with aniline with the MYT equation. The best regression equations obtained are ... 

The various factors that influence reactivity in these types of molecules are clearly illustrated in a study193 of their reactions with methyl iodide and p-nitrophenyl acetate, giving rise in certain cases to deviations from Hammett-type plots. Thus, rates for isoquinoline, pyrimidine, and pyridazine fit reasonably well on to the pK — log Krci (Mel) plot (Fig. 3) and thus conform to the Hammett reaction constant... 

The above interpretation of the results is in agreement with the fact (Abramovich et al., 1958) that in the quaternary ammonium salt (with methyl iodide) of quinaldine dissolved in methanol with methylamine as catalyst, hydrogen exchange reaches 80% in 8 minutes at 18°, while the rate constant for hydrogen exchange in quinaldine itself is k = 3-6 x 10 5 sec-1 at 130°. 

Thiazoles readily undergo AT-alkylation by alkyl halides or tosylates (Menshutkin reaction). The sensitivity of this SN2 quaternization reaction to the molecular environment of the nitrogen atom has been used to evaluate, in a quantitative way, steric and electronic effects of ring substituents. The electronic effect of alkyl substituents (unperturbed by any steric effect) may be evaluated from the rate constants for the reaction of 5-alkylthiazoles with methyl iodide (in nitrobenzene at 30 °C) Table 19 shows that introducing a methyl group at the 5-position corresponds to an acceleration of the rate by a factor of 2 but that each addition of a methyl ramification to the 5-alkyl group enhances the rate only by a factor of 1.1. The data in Table 19 fit well with a Hammett-Taft equation (3) ... 

The effect of transfer, from dimethylacetamide or dimethylformamide to 88 % MeOH-HgO or methanol, on a number of chemical processes involving bromide ion, such as the equilibrium constant for (31), the forward rate constant for (31) (Mac et al., 1967), the rate constant for reaction of bromide ion with methyl iodide (Parker, 1966), or with 2,4-dinitroiodobenzene (Parker, 1966), the redox potential of the Br /Brj couple (Parker, 1966), and the association constant for Br formation (Parker, 1966), can all be accounted for on the assumption that o/Br- is ca. 10 and that solvent activity coefficients of other species which are involved in the processes are unity or cancel each other. 

Fig. 9. Linear Free Energy Relationship between acid dissociation constants of HY, expressed as concentration quotients, (logiCj/K ) (Clare et at, 1966) at 20-25°C and relative rates of reaction of Y with methyl iodide (logA /fc°) at 0°C (Cook et at, 1966 Parker, 1966) in DMF and in methanol.

The reaction of substituted benzyldimethylamine with methyl iodide has the following rate constants in acetonitrile and chlorobenzene at 30° (Table 2). ° Graph the Hammett relationships and comment on the relative values of the Hammett slopes. 

Characteristically, transition metal nucleophiles react much faster with methyl iodide than with methyl tosylate. Rate constant ratios ranging from 30 to 3 X 105 have been found (3). Such behavior qualifies transition metal complexes to be called supersoft nucleophiles (5). Even larger ratios are found for reagents such as Co(CN)53, up to 109. Such large ratios are found only for free-radical pathways (6) and may be used as a mechanistic probe. 

The data in Table III show excellent self-consistency for the three aromatic rate constants, the individual values of which are nevertheless quite different. Comparison with rate constants determined by iodide ion competition kinetics (21) indicates that the absolute values determined in this work are higher for benzene, ethyl alcohol, and methyl alcohol. Comparison with the rate constants determined by thiocyanate ion competition kinetics (1,2) indicates that our absolute values are higher for benzene, benzoate ion, methyl alcohol and ethyl alcohol. This comparison indicates that the actual rate constants for Reactions 3 and 4 may be higher than the values which have been determined (I, 2, 21) from the formation curves of the optically absorbing product by as much as a factor of 1.6 to 2.3 in the former case and 1.7 in the latter case. That is, the true values may be nearer = 2 X 1010 and k4 = 1.2 X 1010 M"1 sec."1 at 25 °C. This same qualitative conclusion for the case of thiocyanate has recently been reached by a different method by Baxendale and Stott (7) whose suggested value for k4 is approximately 2 X 1010M 1 sec."1. The difficulties in the direct absolute determination lie in the complexities of the kinetics and hence in the interpretation of the formation rate curves. 

In most equilibrium-based analytical methods, the success or failure of a determination is not affected by the reaction mechanism, provided that the reaction is either quantitative or the measured parameter at equilibrium is linearly proportional to the initial concentration of the species of interest. This is not the case in reaction-rate methods. Any development of a kinetic method should include, if possible, a complete study of the reaction mechanisms involved in the procedure. (Unfortunately, some reactions, such as catalytic reactions, are so complicated that complete elucidation of the mechanism is impossible.) It should also include a detailed study of the effects of typical sample-matrix components, which can act as catalysts, induce side-reactions, alter the activity of the reactants, and so on. The rates and rate constants for chemical reactions are very sensitive to low concentrations of such spectator species hence, samples containing the same true initial composition of the species of interest but coming from different sources can very often give quite different apparent concentrations. Unless the experimenter is aware of the total reaction mechanism and of all possible factors that can affect either the activation energy or the reaction path, erroneous analytical results can be obtained. A detailed investigation of the simultaneous, in situ, analysis of binary amine mixtures illustrates this point. (Most systems, by the way, are less error-prone than this one.) The rate constants for the reaction of many individual organic amines with methyl iodide in acetone solvent... 

The appHcation of method (2), instantaneous rate constant analysis, for the reaction ofphenoxide ion with methyl iodide in acetonitrile is illustrated in Figure 1.2. Here, we see that the plot on the left of feiRc time falls... 

Fig. 10. Hammett correlation between a-values and the logarithms of the relative rate constants of the S 2 alkylation reaction of substituted pyridinium-N-phenoxides with methyl iodide in chloroform at 25°C Ig (k /k q) = 0.40 a + 0.0003...

Fig. 11. Non-correlation between the Erp-values and the logarithms of the rate constants of the S 2 alkylation reaction of 2,4,6-triphenyl-N-(2,6-diphenyl-4-phenoxide)-pyridinium betaine with methyl iodide, measured in 15 solvents at 25°C (26).

Relative Rate Constants (k i) for the Reaction of Chloride with Methyl Iodide ... 

The correlation of reaction rates with dielectric properties is a well-established approach to the diagnosis of mechanism. Most recent examples of this deal with mixed aqueous solvents (see below), but logarithms of second-order rate constants for oxidative addition of methyl iodide or of oxygen to rraw-[IrCl(CO)(PPh3)2] have been found to correlate with the dielectric constant function (D —l)/(2i) + 1). However, the correlation of these rate constants with the empirical Ex values for the respective solvents, mentioned above, is better. 

---