Sn2 nucleophilic displacement

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... 

SN2 nucleophilic displacements at the silicon atom are much more facile, particularly with elements which are more electronegative. Compounds of the type R3SiX (X = leaving group) hydrolyse rapidly in aqueous solutions. 

The displacement of a tosylatc group in optically active compounds has given access to the preparation of ( —)-/ -2-fluorooctane (4) from ( + )-5 -2-oetyltosylate (3). The SN2 nucleophilic displacement with inversion has been conveniently earried out by using potassium fluoride in triethylene glycol.143 The product is formed in 100% optieal purity, but is contaminated with a mixture of octenes which can easily be removed. 

The reactions of ATP are generally Sn2 nucleophilic displacements (p. E.8), in which the nucleophile may be, for example, the oxygen of an alcohol or carboxylate, or a nitrogen of creatine or of the side chain of arginine or histidine. Each of the three phosphates of ATP is susceptible to nucleophilic attack (Pig. 13-10), and each position of attack yields a different type of product. 

The first reaction stage is undoubtedly SN2 nucleophilic displacement of chlorine by the ethyl acetoacetate anion. Chlorine bond to carbon is weaker than that of fluorine. The resulting ethyl 5-fluoropentan-2-one-3-carboxylate subsequently cyclizes by an SNi reaction, displacing this time the fluorine atom [73]. 

A typical example of such reactions is the exothermic Sn2 nucleophilic displacement reaction Cl -I- CH3—Br Cl—CH3 - - Br . Table 5-2 provides a comparison of Arrhenius activation energies and specific rate constants for this Finkelstein reaction in both the gas phase and solution. The new techniques described above cf. Sections 4.2.2 and 5.1) have made it possible to determine the rate constant of this ion-molecule reaction in the absence of any solvent molecules in the gas phase. The result is surprising on going from a protic solvent to a non-HBD solvent and then further to the gas phase, the ratio of the rate constants is approximately 1 10 10 The activation energy of this Sn2 reaction in water is about ten times larger than in the gas phase. The suppression of the Sn2 rate constant in aqueous solution by up to 15 orders of magnitude demonstrates the vital role of the solvent. 

To create an LFER for nucleophilicity, Swain and Scott defined the reference reaction to be the Sn2 nucleophilic displacement of bromide from methyl bromide by the reference nucleophile water. A more widely accepted scale based upon methyl iodide is now used (Eq. 8.43). Eq. 8.44 shows the LFER, with rix as the parameter for nucleophile X, and s is the sensitivity parameter for any new reaction under study. Additionally, fcnew, nucx is the rate constant for the new reaction under study with each nucleophile X, while new, Hpis the rate constant for the same reaction with water as the nucleophile. Table 8.5 gives a series of x values for various nucleophiles (based upon CH3I), and the pX s of the conjugate acids. Note, as discussed above, that the pK s do not necessarily correlate with the nucleophilicities, and that the effects of resonance on nucleophilicity are well accounted for with the n values (compare the n values for acetate, phenoxide, and methoxide). 

In the submonomer approach, peptoids are synthesized from the C to N terminus on a Rink amide linker resin using a two-step coupling cycle (Fig. 2). First step involves a DIC-mediated coupling of bromoacetic acid to the resin followed by a SN2-nucleophilic displacement by a primary amine. This cycle is repeated until the desired compound is obtained. The peptoid is then cleaved from the resin with 95 % aqueous TFA. Following removal of TFA by evaporation, the peptoid is precipitated and lyophilized. Finally, the identity of the product is verified by chromatography combined... 

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