Nucleophilic Substitution Reactions: Mechanisms, Factors, and Importance, Study notes of Chemistry

Download Nucleophilic Substitution Reactions: Mechanisms, Factors, and Importance and more Study notes Chemistry in PDF only on Docsity! 1 Nucleophilic Substitution Reactions One atom or group is replaced with another atom or group: e.g. These reactions are called nucleophilic substitution reactions and are typical of alkyl halides (1-bromobutane shown here is an alkyl halide). The first reaction allows the preparation of an alcohol from an alkyl halide. It is an important reaction. The last reaction allows the formation of a molecule with one more carbon in the chain. This is also a vary important reaction. In the exmples above the groups above the arrows (hydroxyl, chloride and cyanide) are the nucleophiles. In all three cases they are negatively charged (a nucleophile can be neutral). The nucleophiles attack the carbon to which bromine is attached. This carbon is called an electrophilic center. The bromine atom is called the leaving group. Leaving groups are typically electronegative. Nucleophiles are typically electronegative. There are two ways by which this displacement reaction or substitution occurs. (1) SN 2 The attacking nucleophile comes from one side and the leaving group leaves from the other at the same time. When the leaving group is halfway gone the new incoming group (nucleophile) is halfway in. This is a bimolecular substitution reaction because both the molecule and the nucleophile are involved in the process at all stages. SN 2 stands for substitution-nucleophilic-bimolecular. In an SN 2 reaction the rate depends on the concentration of both the reactant and the nucleophile. Both are involved in the transition state of the rate determining step. If the center being attacked by the nucleophile is chiral, it maintains chirality at the end of an SN 2 process even though it may switch from R to S or vice versa because the new group goes in opposite to the position of the former group that it replaced. Whether the R /S designation really changes depends on the priority (remember the Cahn Ingold, Prelog rules) of the incoming group (nucleophile) relative to that of the leaving group. (2) SN 1 The leaving group leaves without the involvement of the incoming nucleophile. In other words the molecule dissociates spontaneously into a positively charged Br OH- OH Br Cl Cl- Br CN CN- + Br- + Br- + Br- 2 carbon species and a negatively charged leaving group to form a pair of ions. The incoming nucleophile can attack this positive species (called a carbocation) which is planar from any side since the leaving group has already left and is not blocking attack from one side as it would in a bimolecular process. This is called a unimolecular process. SN 1 stands for substitution-nucleophilic-unimolecular. In an SN 1 reaction the rate depends on the concentration of the reactant only. If the center at which the substitution is taking place is chiral, the stereochemistry gets scrambled after the displacement (the product is racemic) because there is control of the direction of attack. A flat species can be approached from either side with the same ease or difficulty. The rate of reaction of an alkyl halide by an SN 2 process is slower the size of the alkyl group involved. Primary alkyl halides react rapidly, secondary much more slowly and tertiary very, very slowly. This is because of a phenomenon called steric hindrance. This simply means blocking because of size. More substituents or bigger substituents around the carbon to be attacked make it more difficult for the nucleophile to “get through” to attack. This makes the reaction slower. Methyl halides are the most reactive because there are no alkyl groups blocking attack of the carbon to be substituted. Of the halides, iodide is the easiest to displace then bromide then chloride then fluoride (which is very difficult to displace). For this reason, iodides and bromides are used the most often in synthetic organic chemistry. Generally, the larger the atom, the greater the distance between the two bonded centers, the less tightly the electrons are shared, the easier it is to break the bond. This can also be rationalized based on basicity. Solvent effects: In order for a nucleophile to participate in a reaction it must dissolve and be available in an ionized (or at least partially ionized) form. The smaller an ion, the greater the charge density (charge divided by volume) the more pronounced its ionic properties and the less likely that it will be freely dissociated unless the solvent were extremely polar like water. Because of this, iodide (small charge density) can exist easily in organic solvents and function as a nucleophile and fluoride cannot and is poor at nucleophilic displacement reactions. The sequence is iodide is better than bromide is better than chloride is better than fluoride. For obvious reasons, this also reflect the ease of displacement of the halogens. In an SN 1 reaction, the reacting molecule (in this case an alkyl halide) must dissociate into two charged species. If the carbocation is well stabilized because it is tertiary, benzylic or allylic it will exist relatively easily in an organic solvent especially if the solvent is polar and therefore has a high dielectric constant. This is also aided if the charge density of the leaving group is small (for instance iodide) and requires less stabilization by interaction of the solvent (solvation). The SN 1 process dominates if the carbocation is tertiary, benzylic or allylic and