Halogenoalkanes, nucleophilic substitution

The mechanism of nucleophilic substitution in primary halogenoalkanes proceeds as follows, using 1-bromobutane as an example ... 

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. 

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 is in fact another mechanism by which the nucleophilic substitution of halogenoalkanes can be achieved. The major factor that determines which mechanism takes place in a particular case is thought to depend primarily on the structure of the halogenoalkane. 

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. 

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

Consider now the action of the solvent in the context of the two different mechanisms of nucleophilic substitution. Any formation of a solvent shell around the nucleophile is in the way, holding back the nucleophile from attacking the halogenoalkane. For the nucleophile to do its job, the nucleophile must first shed this solvent shell. This is always the case when a nucleophile is dissolved in a polar protic solvent, but not so when a polar aprotic solvent is used. 

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. 

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 ... 

As we have seen earlier when considering the S l mechanism for the nucleophilic substitution of halogenoalkanes, carbocations can be characterized as primary, secondary or tertiary. Tertiary carbocations are the most energetically stable, with primary carbocations being... 

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 ... 

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. 

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

The Sj.jl mechanism and the Sj 2 mechanism are both likely to play a part in the nucleophilic substitution of secondary 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 in terms of mechanisms and discussion of primary, secondary and tertiary halogenoalkanes. There is also a video showing mechanism of nucleophilic substitution on this site. 

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

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. 

Some of the experimental evidence on which halogenoalkanes are most susceptible to nucleophilic attack has been gained using an aqueous silver nitrate solution as the source of the nucleophile. The solvent, water, is the nucleophile. The usefulness of this approach is that the appearance of the released halide ion is immediately detected by precipitation with the silver ions. Figure 20.13 shows the precipitates produced as a result of adding halogenobutanes (RCl, RBr and Rl) separately to silver nitrate solution. The precipitates seen here are (left to right) silver chloride, silver bromide and silver iodide. The time taken for the precipitate to appear may be used as a comparative measure of the ease with which the substitution occurs. 

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. 

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