Part 5 REACTIVITY

• Reaction schemes aren't always written as balanced reactions; byproducts are sometimes left out to highlight the desired organic product.
• In a substitution reaction, one part of a molecule (the leaving group) is substituted for a new part (the nucleophile).
• Substitution reactions involve an electrophile (accepts electrons), a nucleophile (donates electrons) and a leaving group (the part of the electrophile that is replaced). In the desired organic product, there is a new bond between the electrophile and nucleophile.

In an S_N2 reaction:

• The mechanism occurs in a single elementary step.
• The reactive carbon in the electrophile is the one directly bonded to the leaving group.
• The nucleophile approaches the electrophile from the side opposite to the leaving group.
• The kinetics follow the same principles as a standard bimolecular elementary reaction.

In an S_N2 reaction:

• Electrophiles with fewer branches close to the reactive carbon react more quickly.
• Negatively charged nucleophiles react more quickly than neutral nucleophiles.
• Within the same row of the periodic table, nucleophiles with less electronegative nucleophilic atoms tend to react more quickly.
• Sterically bulky nucleophiles tend to react less quickly.
• Groups that leave as weaker bases generally make better leaving groups.

• When an S_N2 reaction occurs at an asymmetric carbon on the electrophile, the product's stereochemistry is inverted relative to the reactant.
• The stereochemistry only inverts at the electrophile's reactive carbon, not distance stereocentres.

• S_N1 reactions occur over two elementary steps: (1) the leaving group leaves, then (2) the nucleophile adds.
• When an S_N1 reaction occurs at an asymmetric carbon on the electrophile, the products with inverted and retained relative stereochemistry are both produced.
• The first step (when the leaving group leaves) is the rate determining step

In an S_N1 reaction:

• More substituted electrophiles react more quickly because they lead to more stable carbocation intermediates.
• Anionic and neutral nucleophiles react at similar rates.
• Weaker bases generally make better leaving groups.

• Adding an acid catalyst increasing the rate of S_N1 reactions with poor leaving groups such as HO^- or RO^-.
• The acid-catalyzed S_N1 mechanism involves four key steps: (1) an initial acid/base step to improve the leaving group, (2)/(3) the standard steps of an S_N1 mechanism, and (4) a final acid/base step to give the neutral product.

• In substitution reactions, methyl and 1° electrophiles react via the S_N2 mechanism only, 3° electrophiles react via the S_N1 mechanism only.
• 2° electrophiles can react via both the S_N1 and S_N2 mechanisms. To determine/control which mechanism dominates:
  • Anionic nucleophiles favour the S_N2 mechanism, while neutral nucleophiles favour the S_N1 mechanism.
  • High nucleophile concentrations favour the S_N2 mechanism, while low nucleophile concentrations favour the S_N1 mechanism.
  • Polar aprotic solvents favour the S_N2 mechanism, while polar protic solvents favour the S_N1 mechanism.
• If the product shows relative inversion of stereochemistry (only), then the S_N2 mechanism dominated; if both stereoisomers are formed, then the S_N1 mechanism was favoured.