Base strength elimination versus

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

Ejfect of Solvent on El versus E2 versus ElcB. With any reaction a more polar environment enhances the rate of mechanisms that involve ionic intermediates. Eor neutral leaving groups, it is expected that El and ElcB mechanisms will be aided by increasing polarity of solvent and by increasing ionic strength. With certain substrates, polar aprotic solvents promote elimination with weak bases (the E2C reaction). 

Chapters 11 and 12 discuss reactions of alkyl halides to give either substitution or elimination products. It is clear from Chapter 12 that elimination occurs when the nucleophile is also a strong base and when substitution is inhibited due to steric hindrance. There are many cases in which substitution and elimination compete, particularly when the substrate is a secondary alkyl halide. The solvent plays an important role in these reactions, and solvent identification is a key parameter for distinguishing bimolecular versus unimolecu-lar (ionization) processes. The nature of the alkyl halide (1°, 2°, or 3°) is important, as is the strength of the nucleophile and whether or not that nucleophile can also react a strong base. This chapter will discuss those factors that influence both substitution and elimination, as well as introduce several assumptions that will help make predictions as to the major product. 

For a secondary halide in a reaction with a base, with water as the solvent, ionization is a competitive process. Most of the time, the 8 2 is faster than the Sf fl reaction because direct attack at the a-carbon is more facile than ionization, but the extent of direct substitution versus ionization and then trapping with a nucleophile depend on the strength and nature of the nucleophile. If the nucleophile is a weak base, the Sn2 reaction will dominate in an aprotic solvent. If the nucleophile is a strong base, elimination competes with substitution, and a mixture of Sn2 and E2 products is predicted. In water, it is not obvious whether ionization will lead to the major product, although it is assumed that in aqueous media the 8 1 reaction will dominate. 

---