Electrophilic Substitution

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Electrophilic Substitution : Electrophilic substitution reactions are chemical reactions in which an electrophile displaces another group, typically but not always hydrogen. Electrophilic substitution is characteristic of aromatic compounds. Electrophilic aromatic substitution is an important way of introducing functional groups on benzene rings. The other main reaction type is electrophilic aliphatic substitution. Electrophilic aromatic substitution The most important reactions of this type that take place are aromatic nitration, aromatic halogenation, aromatic sulfonation and acylation and alkylating FriedelCrafts reactions. Electrophilic aliphatic substitution In electrophilic substitution in aliphatic compounds, an electrophile displaces a functional group. This reaction is similar to nucleophilic aliphatic substitution where the reactant is a nucleophile rather than an electrophile. The two electrophilic reaction mechanisms, SE1 and SE2 (Substitution Electrophilic), are also similar to the nucleophile counterparts SN1 and SN2. In the SE1 course of action the substrate first ionizes into a carbanion and a positively charged organic residue. The carbanion then quickly recombines with the electrophile. The SE2 reaction mechanism has a single transition state in which the old bond and the newly formed bond are both present. Nucleophilic Substitution : A nucleophile is an the electron rich species that will react with an electron poor species A substitution implies that one group replaces another. Nucleophilic substitution reactions occur when an electron rich species, the nucleophile, reacts at an electrophilic saturated C atom attached to an electronegative group (important), the leaving group, that can be displaced as shown by the general scheme: The electrophilic C can be recognised by looking for the polar s bond due to the presence of an electronegative substituent (esp. C-Cl, C-Br, C-I and C-O) Nucleophilic substitution reactions are an important class of reactions that allow the interconversion of functional groups. Of particular importance are the reactions of alkyl halides (R-X) and alcohols (ROH) For alcohols, the range of substitution reactions possible can be increased by utilising the tosylates (R-OTs), an alternative method of converting the -OH to a better leaving group. There are two fundamental events in these substitution reactions: formation of the new bond to the nucleophile breaking of the bond to the leaving group Depending on the relative timing of these events, two different mechanisms are

possible: Bond breaking to form a carbocation preceeds the formation of the new bond : SN1 reaction Simultaneous bond formation and bond breaking : SN2 reaction SN1 mechanism SN1 indicates a substitution, nucleophilic, unimolecular reaction, described by the expression rate = k [R-LG] This pathway is a multi-step process with the following characteristics: step 1: rate determining (slow) loss of the leaving group, LG, to generate a carbocation intermediate, then step 2: rapid attack of a nucleophile on the electrophilic carbocation to form a new s bond Multi-step reactions have intermediates and several transition states (TS). In an SN1 there is loss of the leaving group generating an intermediate carbocation which then undergoes a rapid reaction with the nucleophile. The reaction profiles shown here are simplified and do not include the equilibria for protonation of the -OH. General case SN1 reaction The following issues are relevant to the SN1 reactions of alcohols: Effect of RReactivity order : (CH3)3C- > (CH3)2CH- > CH3CH2- > CH3In an SN1 reaction, the key step is the loss of the leaving group to form the intermediate carbocation. The more stable the carbocation is, the easier it is to form, and the faster the SN1 reaction will be. Some students fall into the trap of thinking that the system with the less stable carbocation will react fastest, but they are forgetting that it is the generation of the carbocation that is rate determining. More about carbocations -LG The only event in the rate determining step of the SN1 is breaking the C-LG bond. For alcohols it is important to remember that -OH is a very poor leaving. In the reactions with HX, the -OH is protonated first to give an oxonium, providing the much better leaving group, a water molecule Nu Since the nucleophile is not involved in the rate determining step of an SN1 reaction, the nature of the nucleophile is unimportant. In the reactions of alcohols

with HX, the reactivity trend of HI > HBr > HCl > HF is not due to the nucleophilicity of the halide ion but the acidity of HX which is involved in generating the leaving group prior to the rate determining SN2 mechanism SN2 indicates a substitution, nucleophilic, bimolecular reaction, described by the expression rate = k [Nu][R-LG] This pathway is a concerted process (single step) as shown by the following reaction coordinate diagrams, where there is simultaneous attack of the nucleophile and displacement of the leaving group.

Single step reactions have no intermediates and single transition state (TS). In an SN2 there is simultaneous formation of the carbon-nucleophile bond and breaking of the carbon-leaving group bond, hence the reaction proceeds via a TS in which the central C is partially bonded to five groups. The reaction profiles shown here are simplified and do not include the equilibria for protonation of the -OH. General case SN2 reaction The following issues are relevant to the SN2 reactions of alcohols: Effects of RReactivity order : CH3- > CH3CH2- > (CH3)2CH- > (CH3)3CFor alcohols reacting with HX, methyl and 1o systems are more likely to react via an SN2 reaction since the carbocations are too high energy for the SN1 pathway to occur. -LG Once again the leaving group is a water molecule formed by protonation of the -OH group. -OH on its own is a poor leaving group. Nu Since the nucleophile is involved in the rate determining step, the nature of the nucleophile is very important in an SN2 reaction. More reactive nucleophiles will favor an SN2 reaction. Stereochemistry When the nucleophile attacks in an SN2 reaction, it is on the opposite side to the

position of the leaving group. As a result, the reaction will proceed with an inversion of configuration.