Halogenoalkanes, nucleophilic substitution reactions

The mechanism of a nucleophilic substitution reaction is influenced by the nature of the halogenoalkane, the nucleophile and the solvent. 

Towards the end of Chapter 10 we introduced a classic example of a nucleophilic substitution reaction, namely the hydrolysis of a halogenoalkane by a warm aqueous solution of sodium hydroxide. As a result of the polarization of the carbon-halogen bond, the carbon atom is an electron-deficient centre susceptible to attack by a nucleophile such as the hydroxide ion (OH ). Primary halogenoalkanes are thought to undergo a substitution mechanism that involves a single reaction step. This one-stage reaction involves the simultaneous attack of the nucleophile and departure of the halide ion. We will use as an example the reaction between bromomethane and sodium hydroxide solution ... 

There are various factors that affect the rate of a nucleophilic substitution reaction involving a halogenoalkane ... 

Nucleophilic substitution reactions are important in organic synthesis because the halogen atom on halogenoalkanes can be replaced by other functional groups. The reaction with potassium cyanide is a good illustration of this. The cyanide ion reacts to form a nitrile. For example, bromoethane reacts by an Sj42 mechanism with a solution of potassium cyanide in ethanol to form propanenitrile ... 

When an aqueous solution of sodium hydroxide is added to a halogenoalkane, a nucleophilic substitution reaction takes place. The halogen atom in the halogenoalkane is replaced by an —OH, hydroxyl group, so the organic product formed is an alcohol ... 

There are two possible mechanisms that can operate in the nucleophilic substitution reactions of halogenoalkanes. 

Sj l mechanism the steps in a nucleophilic substitution reaction in which the rate of the reaction (which is determined by the slow step in the mechanism) involves only the organic reactant, e.g. in the hydrolysis of a tertiary halogenoalkane. 

Halogenoalkanes react with nucleophiles in substitution reactions and with bases in elimination reactions. 

The two main mechanisms for nucleophilic substitution of halogenoalkanes (RX) are SnI and 8 2. These represent the extreme mechanisms of nucleophilic substitution and some reactions involve mechanisms which lie somewhere between the two. 

Halogenoalkanes undergo competitive substitution and elimination reactions. The ratio of products derived from substitution and elimination depends on the structure of the halogenoalkane, the choice of base or nucleophile, the reaction solvent and the temperature. Sn2 reactions are normally in competition with E2 reactions, while S jl reactions are normally in competition with El reactions. 

As mentioned above, for primary halogenoalkanes this reaction is a single-step reaction in which two species are involved in the one rate-determining step, and therefore the reaction is said to be bimolecular. The nucleophile (OH ) is attracted to the electron-deficient carbon atom and a transition state is formed in which the carbon-bromine bond is broken at the same time as a new carbon-oxygen bond is formed. The bromine atom then leaves as a bromide ion, and the alcohol (in this case methanol) is formed (Figure 20.3). This mechanism is fully described as an 8 2 (substitution nucleophilic bimolecular) reaction. 

As the slow step of this reaction is determined by the concentration of only one reactant (the halogenoalkane), it is described as a unimolecular reaction. This reaction mechanism is therefore described as an Sf l (substitution nucleophilic unimolecular) reaction. 

The mechanism of nucleophilic substitution in secondary halogenoalkanes is less easy to define as the data show that they usually undergo a mixture of both Sj,] and S),j2 mechanisms, depending on the reaction conditions, or, possibly, some mechanism in between the two. 

Kinetic studies demonstrate that substitution reactions with primary halogenoalkanes proceed by an S[,j2 mechanism. Substitution reactions with tertiary halogenoalkanes, however, proceed by an S[,jl mechanism in which an intermediate carbocation is formed. The reaction is first order with respect to the halogenoalkane, and is independent of the concentration of the nucleophile. It involves two steps. A similar experimental approach to that described above using aqueous silver nitrate solution can be used as part of an investigation to determine the relative rate of substitution of primary, secondary or tertiary bromoalkanes. 

A close look at the nature of a nucleophile will emphasize that it shares common features with a Lewis hase (see Chapter 18). Indeed, a nucleophilic species can act as such a base if the reaction conditions are appropriate - it can remove a proton (H ion) from a halc enoalkane and thereby initiate an elimination reaction. In this type of reaction HX is eliminated from the halogenoalkane and an alkene is produced. It is essential to realize that, given the similarity of the reagents involved, the two processes of nucleophilic substitution and elimination are generally in competition with each other. If a primary halogenoalkane is reacted with aqueous alkali (OH (aq)) then the substitution reaction we have discussed earlier is favoured. However, if ethanolic alkali (OH (ethanol)) is used, then the elimination reaction is favoured. 

The aqueous hydroxide ion behaves as a nucleophile here, because it is donating a pair of electrons to the carbon atom bonded to the halogen in the halogenoalkane. This is why the reaction is called a nucleophilic substitution. 

Many of the reactions of halogenoalkanes are nucleophilic substitutions. In these reactions, the nucleophile attacks the carbon atom bonded to the halogen. Remember from Chapter 14 that nucleophiles are donors of an electron pair and are attracted to electron-deficient atoms. 

---