Hydrolysis kinetics alkyl halides

Kinetics of nongrowth substrate transformation co-reduction and co-hydrolysis of alkyl halides... 

Alkylations of lithiated chiral 4,5-dihydrooxa7oles with 2.0 equivalents of a racemic secondary alkyl halide proceed under kinetic resolution10-16. The (S)-alkyl halide is assumed to react preferentially, and, after quenching with water, the excess (7 )-alkyl halide is isolated in 92-99% purity (determined by GC) and in 5 49% optical purity10. Hydrolysis of the alkylated 4,5-di-hydrooxazoles provides the chiral 3-alkylalkanoic acids in 99-99.8% purity (determined by GC) and 13-47% optical purity10. 

Organonickel(II) species are believed to be formed during the reaction between [Ni(TMC)] and primary alkyl halides, and subsequently undergo hydrolysis with cleavage of the Ni—C bond. Kinetic data measured in the presence of excess alkyl halide indicate a rate law -dlNi1 (TMC)+]/cft = MNi (TMCr][RX]. The rate constants increase for R and X in the order methyl < primary < secondary < allyl < benzyl halides and Cl < Br < I (133, 140). This suggests that the rate-determining step is electron transfer from the Ni(I) complex to R—X via an inner-sphere atom-transfer mechanism (143). 

Addition of excess CH3I to a solution of [Ni (tmc)]+ results in the rapid loss of the absorption (A = 360 nm, e = 4 x 103 M-1 cm-1) and appearance of a less intense band at A = 346 nm. A subsequent slower reaction gives rise to the weaker absorbance profile of [Ni"(tmc)]2+. The data are interpreted in terms of the formation of an organo-nickel(II) species followed by a slower hydrolysis with breaking of the Ni-C bond. Kinetic studies under conditions of excess alkyl halide show a dependence according to the equation — d[Ni1(tmc)+]/cft = 2 [Ni(I)][RX]. The data have been interpreted in terms of a ratedetermining one-electron transfer from the nickel(I) species to RX, either by outer-sphere electron transfer or by halogen atom transfer, to yield the alkyl radical R. This reactive intermediate reacts rapidly with a second nickel(I) species ... 

Oxidation-reduction (redox) reactions, along with hydrolysis and acid-base reactions, account for the vast majority of chemical reactions that occur in aquatic environmental systems. Factors that affect redox kinetics include environmental redox conditions, ionic strength, pH-value, temperature, speciation, and sorption (Tratnyek and Macalady, 2000). Sediment and particulate matter in water bodies may influence greatly the efficacy of abiotic transformations by altering the truly dissolved (i.e., non-sorbed) fraction of the compounds — the only fraction available for reactions (Weber and Wolfe, 1987). Among the possible abiotic transformation pathways, hydrolysis has received the most attention, though only some compound classes are potentially hydrolyzable (e.g., alkyl halides, amides, amines, carbamates, esters, epoxides, and nitriles [Harris, 1990 Peijnenburg, 1991]). Current efforts to incorporate reaction kinetics and pathways for reductive transformations into environmental exposure models are due to the fact that many of them result in reaction products that may be of more concern than the parent compounds (Tratnyek et al., 2003). 

Although superoxide ion is a powerM nucleophile in aprotic solvents, it does not exhibit such reactivity in water, presumably because of its strong solvation by that medium (A//hydration, lOOkcalmol" ) and its rapid hydrolysis and disproportionation. The reactivity of 02 - with aUcyl halides via nucleophilic substitution was first reported in 1970. These and subsequent kinetic studies - confirm that the reaction is first order in substrate, that the rates follow the order primary > secondary > tertiary for alkyl halides and tosylates, and that the attack by 02 - results in inversion of configuration (Sn2). 

Like other alkyl halides, mustard gas (j8,i9 -dichlorodiethyI sulfide) undergoes hydrolysis. But this hydrolysis is unusual in several ways (a) the kinetics is first-... 

The reactivity of O2 - with alkyl halides in aprotic solvents occurs via nucleophilic substitution (Chapter 7).23-25,45 These and subsequent kinetic studies confirm that the reaction order is primary>secondary >tertiary and I>Br>Cl >F for alkyl halides, and that the attack by O2-- results in inversion of configuration (Sn2). Superoxide ion also reacts with CCl4,25,26 Br(CH2)2Br,46 C6Cl6, 2,48 and esters -Sl in aprotic media. The reactions are via nucleophilic attack by O2-- on carbon, or on chlorine with a concerted reductive displacement of chloride ion or alkoxide ion. As with all oxy anions, water suppresses the nucleophilicity of 02 - (hydration energy, 100 kcal)52 and promotes its rapid hydrolysis and disproportionation. The reaction pathways for these compounds produce peroxy radical and peroxide ion intermediates (ROO- and ROO ). 

Finally, several equilibrium and kinetic properties of aldehyde-bisulfite adducts were found to be linearly related Taft s a parameter (Betterton et al.t 1988). These compounds, which include a-hydroxymethane sulfonate and other a-hydroxyalkyl sulfonates, may be important reservoirs of S(IV) species inj clouds, fog, and rain. Fairly good relationships were found between equilibrium properties (e.g. acidity constants) and Sir values, but rates constants for) nucleophilic addition of S03 to the aldehydes showed only a crude fit, Similarly, poor results were found in applying a to hydrolysis reactions of] volatile alkyl chlorides (T. Vogel, University of Michigan, personal communh cation, 1989), and this has been shown to be a general characteristic of reactioni of alkyl halides with nucleophiles (Okamoto et al., 1967). 

Let us now turn to an example of nucleophilic substitution involving a group of pollutants other than alkyl halides. We consider the hydrolysis of thiometon and disulfoton, two insecticides that were among the major contaminants that entered the Rhine River after the famous accident at Schweizerhalle in Switzerland in 1986 (Capel et al., 1988). This example is representative for the hydrolysis of a variety of phosphoric and thiophosphoric acid derivatives (e.g., esters, thioesters, see Fig. 1), and it illustrates that hydrolysis of a more complex molecule may be somewhat more complicated. The kinetic data, as well as the proposed mechanisms of hydrolysis of thiometon and disulfoton, are presented in Table 4 and Figure 2, respectively. In these cases, the base catalyzed reaction... 

They found that the rate of hydrolysis depends only on the concentration of tert-butyl bromide. Adding the stronger nucleophile hydroxide ion, moreover, causes no change in the rate of substitution, nor does this rate depend on the concentration of hydroxide. Just as second-order kinetics was interpreted as indicating a bimolecular rate-determining step, first-order kinetics was interpreted as evidence for a unimolecular rate-determining step—a step that involves only the alkyl halide. 

B.iv. Nitrile Enolates. Nitrile enolates are formed by reaction of a nitrile with LDA or another suitable base. Both alkylation 30 and condensation reactions with aldehydes 3 or ketones are known. 32 in addition to alkyl halides and carbonyl derivatives, condensation can occur with another nitrile. The base-catalyzed condensation of two nitriles to give a cyano-ketone, via an intermediate cyano enolate, is known as the Thorpe reaction. 33.109e Reaction of butanenitrile with sodium ethoxide gave a nitrile enolate, which reacted with a second molecule of butanenitrile at the electrophilic cyano carbon to give 206. Hydrolysis gave an intermediate imine-nitrile (207), which is in equilibrium with the enamine form (208, sec. 9.6.A). Hydrolysis led to the final product of the Thorpe reaction, an a-cyano ketone, 209. 33 Mixed condensations are possible when LDA and kinetic conditions are used to generate the a-lithionitrile (a mixed Thorpe reaction). When pentanenitrile was treated with LDA and condensed with benzonitrile, 2-cyano-l-phenyl-1-pentanone was the isolated product after acid hydrolysis. Nitrile enolates can also be alkylated with a variety of alkyl halides. 34... 

Hydrolysis of primary alkyl halides with aqueous alkali follows S 2 mechanism. For example, methyl chloride undergoes hydrolysis with sodium hydroxide following second order kinetics. 

The discussion and experiments presented below illustrate methods of studying chemical kinetics and determining the effects of structure on reactivity, as exemplified by the solvolysis of tertiary alkyl halides. The term "solvolysis" describes a substitution reaction in which the solvent, HOS, functions as the nucleophile (Eq. 14.30). In principle, solvolyses may be performed in any nucleophilic solvent such as water (hydrolysis), alcohols (alcoholysis), and carboxylic acids (for example, acetolysis with acetic acid). However, a practical limitation in choosing a solvent is the solubility of the substrate in the solvent because the reaction mixture must be homogeneous if it is not, surface effects at the interface of the phases will make the kinetic results difficult to interpret and probably nonreproducible as well. In the experiment described here, you will explore solvolyses in mixtures of 2-propanol and water. 

Kinetics Having already seen that the rate of nucleophilic substitution depends on the leaving group (1 > Br > Cl > F), we know that the carbon-halogen bond must break in the slow step of the reaction and, therefore, expect the concentration of the alkyl halide to appear in the rate law. What about the nucleophile Hughes and Ingold found that many nucleophilic substitutions, such as the hydrolysis of methyl bromide in base ... 

The kinetics and mechanism of the reactions of pyridine-A -oxides with alkyl halides in acetonitrile have been investigated, and also the decompositions of the resulting iV-alkoxypyridinium salts to starting reagents.The acid-catalysed hydrolysis of diazoacetaldehyde has been examined kinetically. ... 

Our compatriot N. A. Menshutkin made a great contribution to the development of the kinetics. In 1877 he studied in detail the reaction of formation and Iqrdrolysis of esters from various acids and alcohols and was the first to formulate the problem of the dependence of the reactivity of reactants on flieir chemical structure. Five years later when he studied the hydrolysis of tert-zmy acetate, he discovered and described the autocatalysis phenomenon (acetic acid formed in ester hydrolysis accelerates the hydrolysis). In 1887-, studying the formation of quaternary ammonium salts from amines and alkyl halides, he found a strong influence of the solvoit on the rate of this reaction (Menschutkin reaction) and stated the problem of studying the medium effect on the reaction rate in a solution. In 1888 N. A. Menschutkin introduced the term chmical kinetics in his monograph Outlines of Development of Chemical Views. ... 

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