Bimolecular Nucleophilic Substitutions

Although certain mechanisms for a reaction can be eliminated on the basis of experimental evidence, it is never possible to prove that the reaction follows a particular mechanism. It can only be demonstrated that all the experimental facts are consistent with that mechanism. One piece of experimental information that is of primary importance is the rate law that the reaction follows. The rate law predicted by a possible mechanism must be consistent with the rate law determined in the laboratory. If the two are not consistent, that mechanism can be ruled out. In the case of these nucleophilic substitution reactions, experimental studies have shown that two different rate laws are followed, depending on the substrate (R—L), the nucleophile, and the reaction conditions. This means that there must be two different mechanisms for the reaction. Let s look at each. 

Investigation of this reaction in the laboratory has shown that the reaction rate depends on the concentration of hydroxide ion and on the concentration of chloroethane (EtCl), that is, the reaction follows the second-order rate law  

From general chemistry you might recall that the dependence of the rate law on the concentration of a particular species requires that species to be involved in the slowest step of the reaction or a step before the slowest step. Therefore, in this case, both hydroxide ion and chloroethane must be present in the slowest step of the reaction. 

This rate law is consistent with mechanism (3), in which the bond to the leaving group (chloride) is broken and the bond to the nucleophile (hydroxide) is formed simultaneously, in the same step. A reaction that occurs in one step is termed a concerted reaction. Because two species (hydroxide ion and chloroethane) are involved in this step, the step is said to be bimolecular. This reaction is therefore described as a bimolecular nucleophilic substitution reaction, or an SN2 reaction. 

What does the transition state for the SN2 reaction look like Because it is a maximum on the free energy versus reaction progress diagram and any change, either forward to products or backward to reactants, is downhill in energy, the transition state has no appreciable lifetime. Because of this, it cannot be observed directly and any information 

When a nucleophile collides with a carbon that is part of a polarized bond bearing a leaving group (an electrophilic carbon), it leads to the transform  

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The large rate enhancements observed for bimolecular nucleophilic substitutions m polai aprotic solvents are used to advantage m synthetic applications An example can be seen m the preparation of alkyl cyanides (mtiiles) by the reaction of sodium cyanide with alkyl halides... 

Given the molecular formula CgHnBr construct a molecular model of the isomer that is a pnmary alkyl bromide yet relatively unreactive toward bimolecular nucleophilic substitution... 

The following section describes a versatile method for preparing either symmetri cal or unsymmetrical ethers that is based on the principles of bimolecular nucleophilic substitution... 

The apphcation of bimolecular, nucleophilic substitution (S ) reactions to sucrose sulfonates has led to a number of deoxhalogeno derivatives. Selective displacement reactions of tosyl (79,85), mesyl (86), and tripsyl (84,87) derivatives of sucrose with different nucleophiles have been reported. The order of reactivity of the sulfonate groups in sucrose toward reaction has been found to be 6 > 6 > 4 > 1. ... 

Nucleophilic Substitution. The kinetics of the bimolecular nucleophilic substitution of the chlorine atoms in 1,2-dichloroethane with NaOH, NaOCgH, (CH2)3N, pyridine, and CH COONa in aqueous solutions at 100—120°C has been studied (24). The reaction of sodium cyanide with... 

The above evidence shows that a high degree of bond-making in the rate-determining step of bimolecular nucleophilic substitutions seems... 

The mechanistic pathway" " can be divided into three steps 1. formation of the activating agent from triphenylphosphine and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) 2. activation of the substrate alcohol 1 3. a bimolecular nucleophilic substitution (Sn2) at the activated carbon center. 

In most cases the alkoxide or phenoxide 1 reacts with the alkyl halide 2 by a bimolecular nucleophilic substitution mechanism ... 

Sfj2 reaction (Section 11.2) A bimolecular nucleophilic substitution reaction. 

For substituted anilines (Thompson and Williams, 1977) and for 1-naphthylamine and a series of derivatives thereof (Castro et al., 1986a), k2 and the ratio Ar 2/Ar3 have been determined for nucleophilic catalysis with Cl-, Br-, SCN-, and SC(NH2)2. The values of k2 correspond fairly well to those found for the diazotization of aniline, but those of Ar 2/Ar3 increase markedly in the above sequence (Table 3-1). As k3 is expected to be independent of the presence of Cl- or Br- and to show little dependence on that of SCN- or thiourea, the increase in k 2/k3 for this series must be due mainly to 2. Indeed, the value of log(Ar 2/Ar3) shows a linear correlation with Pearson s nucleophilicity parameter n (Pearson et al., 1968). This parameter is based on nucleophilic substitution of iodine (as I-) in methyl iodide by various nucleophiles. The three investigations on nucleophilic catalysis of diazotization demonstrate that Pearson s criteria for bimolecular nucleophilic substitution at sp3 carbon atoms are also applicable to substitution at nitrogen atoms. 

Bimolecular nucleophilic substitutions of octahedral cobalt complexes. S. C. Chan and J. Miller, Rev. Pure Appl. Chem., 1965, 15, 11-22 (21). 

The reaction of Sn2, that is, the bimolecular nucleophilic substitution with allyl rearrangement... 

The mechanism of these bimolecular nucleophilic substitution reactions is shown in Scheme 11.3 for the reaction between a primary amine and the intermediate dichlorotriazine. A corresponding scheme can be drawn for reaction of a secondary amine, an alcohol or any other nucleophile in any of the replacement steps. It follows from this mechanism that the rate of reaction depends on ... 

As can be seen from the data presented, the high energies of complex formation decrease sharply the endothermicity of the retro-Wittig type decomposition and, moreover, fundamentally change the reaction mechanism. As has been shown for betaines (")X-E14Me2-CH2-E15( + )Me3 (X = S, Se E14 = Si, Ge E14 = P, As), the reaction occurs as bimolecular nucleophilic substitution at the E14 atom. For silicon betaines, the transition states TS-b-pyr with pentacoordinate silicon and nearby them no deep local minima corresponding to the C-b complexes can be localized in the reaction coordinate. 

In this section, we sketch the nature of the three VB state framework as a template to describe bimolecular nucleophilic substitutions ( S. -2)[7, 12, 13], Although it remains to be seen if three VB states are sufficient to describe the title reaction system in solution, this is still a useful additional exercise to expose the reasoning underlying the practical application of our theory. The wave function to describe the Sa/2 reaction... 

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