Nucleophilic substitution reaction, first-order

The evidence that convinced chemists about these two mechanisms is kinetic it relates to the rate of the reactions. It was discovered, chiefly by Hughes and Ingold in the 1930s, that some nucleophilic substitutions are first-order, that is, the rate depends only on the concentration of the alkyl halide and does not depend on the concentration of the nucleophile, while in other reactions the rate depends on the concentrations of both the alkyl halide and the nucleophile. How can we explain this result In the 5 2 mechanism there is just one step, the Sn2 mechanism reaction of n-BuBr with hydroxide ion... 

According to this mechanism, there is a first-order dependence on both the concentration of [ A B] and B, and the reaction is called an SN2 process (substitution, nucleophilic, second-order). Although many nucleophilic substitution reactions follow one of these simple rate laws, many others do not. More complex rate laws such as... 

We have examined the competing isomerization and solvolysis reactions of 1-4-(methylphenyl)ethyl pentafluorobenzoate with two goals in mind (1) We wanted to use the increased sensitivity of modern analytical methods to extend oxygen-18 scrambling studies to mostly aqueous solutions, where we have obtained extensive data for nucleophilic substitution reactions of 1-phenylethyl derivatives. (2) We were interested in comparing the first-order rate constant for internal return of a carbocation-carboxylate anion pair with the corresponding second-order rate constant for the bimolecular combination of the same carbocation with a carboxylate anion, in order to examine the effect of aqueous solvation of free carboxylate anions on their reactivity toward addition to carbocations. 

In order to study the reaction profile for a nucleophilic substitution reaction (76), we first choose our basis set of VB configurations. The major configurations are obtained by rearranging the four key electrons which govern the reaction in all possible, energetically sensible forms. These are indicated... 

Depending on the relative nucleophilicities, [Nu]50% ranges from micromolar to molar concentrations (Table 13.5). Although these values represent only order-of-magnitude estimates, they allow some important conclusions. First, in uncontaminated freshwa-ters (where bicarbonate typically occurs at about 10"3 M, chloride and sulfate occur at about 10 4 M, and hydroxide is micromolar or less, Stumm and Morgan, 1996), the concentrations of nucleophiles are usually too small to compete successfully with water in SN2 reactions involving aliphatic halides. Hence the major reaction will be the displacement of the halide by water molecules. In salty or contaminated waters, however, nucleophilic substitution reactions other than hydrolysis may occur Zafiriou (1975), for example, has demonstrated that in seawater ([CL] 0.5 M) an important sink for methyl iodide is transformation to methyl chloride ... 

The base hydrolyses of PtCl(NH3) + and c/s-PtCl2(NH3)4+ are possibly examples of nucleophilic substitution reactions 204 these remain the only cases which have not been proven otherwise. These reactions follow a rate law which is first order in the platinum(IV) complex, and a hydroxide ion dependence which is intermediate between zero and first order. The reaction is not catalyzed by Pt(NH3)2+. 

The HMPA adducts of trimethylchlorosilane (32, R = Me) and trimethylbromosilane were isolated and found to be ionic as shown. If the first step shown in equation 14 is a pre-equilibrium, the observed order for substitution is first order as expected. For racemization, the rate-limiting step is invertive attack of the second HMPA molecule on 32, such that the reaction is second-order overall with respect to nucleophile. 

Experimental data from nucleophilic substitution reactions on substrates that have optical activity (the ability to rotate plane-polarized light) shows that two general mechanisms exist for these types of reactions. The first type is called an S 2 mechanism. This mechanism follows second-order kinetics (the reaction rate depends on the concentrations of two reactants), and its intermediate contains both the substrate and the nucleophile and is therefore bimolecular. The terminology S 2 stands for substitution nucleophilic bimolecular. ... 

First-Order Reactions First-order nucleophilic substitution requires ionization of the halide to give a carbocation. In the case of a benzylic halide, the carbocation is resonance-stabilized. For example, the 1-phenylethyl cation (2°) is about as stable as a 3° alkyl cation. 

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). 

Equation [2] illustrates a similar nucleophilic substitution reaction with a different alkyl halide, (CH3)3CBr, which also leads to substitution of Br by CH3COO . Kinetic data show that this reaction rate depends on the concentration of only one reactant, the alkyl halide that is, the rate equation is first order. This suggests a two-step mechanism in which the rate-determining step involves the alkyl halide only. 

Originally the difference between unimolecular and bimolecular substitution reactions was deduced from kinetic studies on a wide range of reagents. It was observed that for some reactions the overall rate of substitution depended only upon the concentration of the substrate, i.e. the species undergoing substitution, and that the rate was independent of the concentration of the attacking species, i.e. the nucleophile. The reaction, therefore, is a first order reaction that is, the sum of the indices of the concentration of the reagents in the rate equation equals one. These reactions are called unimolecular nucleophilic substitution reactions, and are given the label SN1. 

After this work, a further elegant experiment was carried out by Hughes et al.,2 with the measurement of the second-order rate constant for a concerted nucleophilic substitution reaction, and this was done in two ways. The substrate was one enantiomer of 2-iodooctane (7) and the nucleophile was radioactive iodide anion, 1, in propanone (acetone). The nature of the reaction is outlined in Scheme 7.4. Firstly, the rate constant was determined polarimetrically to give a rate constant ka then the rate constant for exchange of I was determined this is represented by kex. The ratio of these rate constants within experimental error was 2 1. 

This mode of reaction is also characteristic of solvolytic and first-order nucleophilic substitution reactions ( 1). They will be discussed in Chapter 4. 

As with nucleophilic substitution reactions, rates of dehydrohalogenation reactions will be dependent on the strength of the C-X bond being broken in the elimination process. Accordingly, it is expected that the ease of elimination of X will follow the series Br>Cl>F. The relative reactivities of Br and Cl toward elimination is evident from the hydrolysis product studies of 1,2-dibromo-3-chloropropane (DBCP Burlinson et al., 1982). DBCP has been used widely in this country as a soil fumigant for nematode control and has been detected in groundwaters (Mason et al., 1981) and subsoils (Nelson, et al., 1981). Hydrolysis kinetic studies demonstrated that the hydrolysis of DBCP is first order both in DBCP and hydroxide ion concentration above pH 7. Below pH 7, hydrolysis occurs via neutral hydrolysis however, the base-catalyzed reaction will contribute to the overall rate of hydrolysis as low as pH 5. Product studies performed at pH 9 indicate that transformation of DBCP occurs initially by E2 elimination of HBr and HCl (Figure 2.4). 

The above constants are usually only used in discussions of nucleophilic substitution reactions at saturated carbon. In other reactions a quantity known as the effective molarity is frequently used as a measure of anchimeric assistance. This can be determined only if the rate constant for an analogous intermolecular reaction has been measured. Consider two analogous reactions, one intramolecular [Eq. (10)] and one intermolecular [Eq. (11)]. These are, respectively, first- and second-order pro-... 

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