Substitution reactions: A summary

Table of Contents

• Definition

• SN1 vs SN2 reactions

  • Mechanisms

  • Stereochemistry of products

• Deciding Between SN1 and SN2

  • Factor 1: The electrophile

  • Factor 2: The nucleophile

  • Factor 3: The leaving group

  • Factor 4: The solvent 

Definition

Alkyl halides commonly undergo nucleophilic substitution (SN) reactions in which a nucleophile replaces the halogen. 

S_N1 vs S_N2 reactions

There are two main types of nucleophilic substitution (SN) reactions, commonly referred to as S_N1 and S_N2. These labels denote the mechanisms by which these reactions occur. 

Mechanisms

S_N2 - Substitution Nucleophilic Bimolecular 

In S_N2 reactions, everything happens in one step. A nucleophile attacks the alkyl halide, causing the loss of a leaving group in a single rate-determining step. Therefore, Rate = k [Nucleophile] [alkyl halide]

S_N1 - Substitution Nucleophilic Unimolecular 

In S_N1 reactions, the process occurs in two main steps: first, the leaving group exits, forming a carbocation; then, this carbocation is quickly attacked by a nucleophile. The first step of the reaction is the slowest and determines the overall rate because forming a carbocation, an unstable species, requires a lot of energy. Therefore, Rate = k [alkyl halide]

Stereochemistry of products

In an S_N2 reaction, the nucleophile attacks from the opposite side of the leaving group, leading to an inversion of configuration.

In contrast, the carbocation intermediate formed in an S_N1 reaction can be attacked from either side, leading to both inversion of configuration and retention of configuration.

Deciding Between S_N1 and S_N2

Factor 1: The electrophile

Compounds that form relatively stable carbocations generally react by the S_N1 mechanism, while those that do not form stable carbocations react by the S_N2 mechanism.

S_N2 only

S_N1 or S_N2

S_N1 only

Factor 2: The nucleophile

Strong nucleophiles favor S_N2 reactions. Strong nucleophiles are typically negatively charged and highly polarizable due to size.

Weak nucleophiles do not favor S_N2 reactions allowing S_N1 reactions to compete successfully.  

Factor 3: The leaving group

Both S_N1 and S_N2 reactions depend on the quality of the leaving group. If the leaving group is poor, neither reaction will proceed. S_N1 reactions are generally more sensitive to the leaving group because the rate-determining step of an S_N1 reaction involves the loss of a leaving group.

Some common good leaving groups are halides with iodine being the best leaving group.

Other good leaving groups include sulfonate ions which are resonance stabilized and water.

Bad leaving groups include:

Bad leaving groups can be converted to good ones when treated with a strong acid.

Factor 4: The solvent 

Polar aprotic solvents favor S_N2 reactions. Aprotic solvents do not contain N-H or O-H bonds.

Polar protic solvents contain N-H or O-H bonds and favor S_N1 reactions. The solvents used in S_N1 reactions also function as nucleophiles.