Sn2 Nucleophiles

Sn2 reactions are triggered by the collision of an alkyl halide with a nucleophile. 

Since nucleophilic atoms have nonbonding electrons they can be identified by inspection of Lewis structures. Draw Lewis structures of triraethylamine, methyl fluoride, and phenol. Draw all nonbonding electron pairs and identify all nucleophilic atoms. 

Nucleophilic atoms can also be identified by inspection of electrostatic potential maps. Reactive sites appeal as negative electrostatic potentials. Examine electrostatic potential maps for trimethylamine, methyl fluoride, and phenol. Identify the most nucleophilic atom in each molecule. Are these the same as you identified above using Lewis structures Are all sides of the nucleophilic atoms equally electron rich, or only particular regions  

Enhanced nucleophilicity is often correlated with more negative electrostatic potential. Which of the three molecules listed above is most nucleophilic according to this criterion Which is least nucleophilic (The least nucleophilic molecule does not, in fact, undergo Sn2 reactions.) 

Nucleophiles can also act as acids and bases, and this behavior substantially alters their nucleophilicity. At pH 5, trimethylamine exists mainly as its conjugate acid, trimethylammonium cation. First draw a Lewis structure, and then examine the electrostatic potential for trimethylammonium ion. On the basis of the map, which is the better nucleophile, the cation or the corresponding neutral amine At pH 12, phenol exists mainly as its conjugate base, phenoxide anion. First draw a Lewis structure (or series of Lewis structures), and then examine the electrostatic potential map for phenoxide anion. Which is the better nucleophile, phenoxide or phenol  

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The cleavage reaction occurs in three steps O protonation of the epoxide, Sn2 nucleophilic attack on the protonated epoxide, and deprotonation of the ring-opened product. Draw the complete mechanism. How many intermediates are there Which step determines diol stereochemistry ... 

Sn2 nucleophilic aromatic substitution 2. The intermediate complex mechanism... 

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

Because the Sn2 nucleophilic substitution of uncharged amines with uncharged aliphatic organic halides involves a transition state that is more polar than that of the starting materials, such substitution reactions... 

Gas-phase SN2 nucleophilic substitution reactions are particularly interesting because they have attributes of both bimolecular and unimolecular reactions.1 As discovered from experimental studies by Brauman and coworkers2 and electronic structure theory calculations,3 potential energy surfaces for gas-phase SN2 reactions of the type,... 

Figure 1. Reaction path potentials for the ClI + ChhClb - CUCH3 + Clb and Cl" + CH3Br —> CICH3 + Br- Sn2 nucleophilic substitutions.

Though statistical models are important, they may not provide a complete picture of the microscopic reaction dynamics. There are several basic questions associated with the microscopic dynamics of gas-phase SN2 nucleophilic substitution that are important to the development of accurate theoretical models for bimolecular and unimolecular reactions.1 Collisional association of X" with RY to form the X-—RY... 

Classical trajectory calculations, performed on the PES1 and PESl(Br) potential energy surfaces described above, have provided a detailed picture of the microscopic dynamics of the Cl- + CH3Clb and Cl" + CH3Br SN2 nucleophilic substitution reactions.6,8,35-38 In the sections below, different aspects of these trajectory studies and their relation to experimental results and statistical theories are reviewed. 

For the Cl" + CH3Clb trajectories on PES1, direct substitution only occurs when the C-Cl stretch normal mode is excited with three or more quanta. For CH3Clb at 300 K, the probability of this vibrational excitation and the rate constant with vibrational excitation is too small to make direct substitution an important contributor to Cl + CH3Clb - ClaCH3 + Cl Sn2 nucleophilic substitution on PES1. However, the direct substitution mechanism may become more important if less... 

A dynamical model for SN2 nucleophilic substitution that emerges from the trajectory simulations is depicted in Figure 9. The complex formed by a collision between the reactants is an intermolecular complex CinterR. To cross the central barrier, this complex has to undergo a unimolecular transition in which energy is... 

Figure 9. Dynamical model for Sn2 nucleophilic substitution. The labels R and P denote the reactant and product sides of the central barrier, respectively.

Additional experimental, theoretical, and computational work is needed to acquire a complete understanding of the microscopic dynamics of gas-phase SN2 nucleophilic substitution reactions. Experimental measurements of the SN2 reaction rate versus excitation of specific vibrational modes of RY (equation 1) are needed, as are experimental studies of the dissociation and isomerization rates of the X--RY complex versus specific excitations of the complex s intermolecular and intramolecular modes. Experimental studies that probe the molecular dynamics of the [X-. r - Y]- central barrier region would also be extremely useful. 

The analytic potential energy surfaces, used for the Cl + CH3Clb and Cl + CHjBr trajectory studies described here, should be viewed as initial models. Future classical and quantum dynamical calculations of SN2 nucleophilic substitution should be performed on quantitative potential energy functions, derived from high-level ab initio calculations. By necessity, the quantum dynamical calculations will require reduced dimensionality models. However, by comparing the results of these reduced dimensionality classical and quantum dynamical calculations, the accuracy of the classical dynamics can be appraised. It will also be important to compare the classical and quantum reduced dimensionality and classical complete dimensionality dynamical calculations with experiment. 

Finally, accurate theoretical kinetic and dynamical models are needed for calculating Sn2 rate constants and product energy distributions. The comparisons described here, between experimental measurements and statistical theory predictions for Cl"+CHjBr, show that statistical theories may be incomplete theoretical models for Sn2 nucleophilic substitution. Accurate kinetic and dynamical models for SN2 nucleophilic substitution might be formulated by introducing dynamical attributes into the statistical models or developing models based on only dynamical assumptions. 

DYNAMICS OF GAS-PHASE Sn2 NUCLEOPHILIC SUBSTITUTION REACTIONS William L. Hase, Haobin Wang, and... 

As B is often a nucleophile as well as a base, elimination is frequently accompanied by one-step, concerted (SN2) nucleophilic substitution... 

In accord with general Eyring TS theory, we may consider every elementary chemical reaction to be associated with a unique A- B supramolecular complex that dictates the reaction rate. In the present section we examine representative TS complexes from two well-known classes of chemical reactions Sn2 nucleophilic displacement reactions... 

Hase, W. L. Simulation of gas-phase chemical reactions Applications to SN2 nucleophilic substitution, Science, 266 (1994), 998-1002... 

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