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SN/E Competition (overall)

The Role of the Base in the SN2 / E2 Competition

Due to the lone electron pair, the base applied in an E2 elimination may basically also act as a nucleophile in a SN2 mechanism.

In an SN2 reaction, the nucleophile attacks the heteroatom-substituted carbon atom inside the molecule. In contrast, the base in an E2 elimination abstracts a proton that is located closer to the periphery of the molecule. SN2 reactions are therefore influenced by steric limitations to a considerably greater degree than E2 eliminations.

The nucleophilicity of a base in an SN2 reaction is reduced to a large degree when the base contains massive, sterically demanding substituents. In this case, the reaction rate of the SN2 reaction is decreased, as the energy of the transition state is increased by the interactions of the sterically demanding nucleophile (base) and the substrate molecule. In contrast, the energy of the transition state of the E2 elimination is influenced by bulky substituents of the base to a noticeably lesser degree.

Thus, for the purpose of controlling the SN2/E2 competition, the following consequences pertaining to the type of base applied result:

Favouring the E2 mechanism

  • In favour of the E2 elimination, as strong as possible, non-nucleophilic bases with bulky, sterically-demanding substituents are usually applied.
  • Some examples of weaker, but, nevertheless, sterically-demanding, non-nucleophilic bases are DBN (1,5-diazabicyclo[4.3.0]nonene) and DBU (1,8-diazabicyclo[5.4.0]undecene).
  • Some examples of particularly strong, non-nucleophilic bases are the lithium dialkylamides LDA (lithium diisopropylamide) and LHMDS (lithium hexamethyldisilazide).
  • When DBN, DBU, LDA, or LHMDS are applied, even chemoselective E2 eliminations with primary and secondary alkyl halogenides may be achieved. This is exceptional, as in these cases the SN2 reaction is normally preferred over the E2 elimination - particularly in the connection with primary alkyl compounds.

Structures of very bulky and sterically demanding bases.

  • The strong and relatively bulky base potassium t-butoxide is also frequently applied to chemoselective (E2 instead of SN2) E2 eliminations, as it is more easily available than LDA, LHMDS, DBN, and DBU.
  • Instead of the special, very bulky and sterically demanding bases LDA, LHMDS, DBN, and DBU that are applied in difficult cases, the more readily available bases hydroxide, alkoxides (also primary and secondary) and amide are often used in E2 eliminations even if they are much less bulky and therefore less chemoselective.

Favouring the SN2 mechanism

  • In order to favour the SN2 reaction and largely prevent the E2 elimination, the base applied must not be too strong. As basicity increaes, nucleophilicity generally increases, as well. This is due to the fact that these two properties are both correlated with the availability of lone, non-bonding electron pairs. However, the basicity usually increases to a higher degree than the nucleophilicity does - that is, with increasing basicity the E2 elimination continuously exceeds the SN2 reaction more and more. This effect is observed even the base is not bulky and sterically demanding. However, it is larger in connection with such a base.
  • SN2 reactions without any considerable E2 eliminations as side reactions can, therefore, only be obtained with good nucleophiles that show a basicity that is as low as possible.
According to general rule, nucleophiles with a lower basicity than that of the hydroxide anion tend to react with primary and secondary alkyl halides, for instance, in an SN2 reaction, while nucleophiles with a higher basicity than that of the hydroxide anion tend to react in an E2 elimination.
  • However, the nucleophile applied in an SN2 reaction cannot be selected as freely as the base in an E2 elimination, since this nucleophile becomes a part of the product molecule, while the base in an E2 elimination does not. Thus, in selecting a suitable nucleopile for an SN2 reaction, one must also keep in mind the product structure for which it is intended.
  • The electrophilic carbon atom in an SN2 reaction reacts particularly well with a soft Lewis base, as it is, in fact, a soft Lewis acid. The best prerequisite for chemoselective (SN2 instead of E2) SN2 reactions is thus the application of relatively weak and soft bases that are also good nucleophiles. These are bases that possess an easily available and polarizable lone electron pair but display just a low basicity (see also HSAB principle). Such bases are, for example, anions such as hydrogensulphide (HS¯), alkyl sulphides (RS¯), iodide (I¯), and cyanide (CN¯).
HS¯  ›  RS¯  ›  ArS¯  ›  I¯  ›  CN¯  ›  OH¯  ›  N3¯  ›  Br¯  ›  ArO¯  ›  Cl¯  ›  AcO¯  ›  H2O

Nucleophilicity of several weak and moderately strongly basic nucleophiles in SN2 reactions.

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