MED-108 Organic Chemistry Reaction Mechanisms PDF

MED-108 Organic Chemistry Organic Reaction Mechanisms LOBs covered Describe the free radical addition reactions that form polymers Identify and write the steps of free radical chlorination of alkanes Write the full mechanism of electrophilic addition of HX to an alkene Write the full mechanisms for...

MED-108 Organic Chemistry Organic Reaction Mechanisms LOBs covered Describe the free radical addition reactions that form polymers Identify and write the steps of free radical chlorination of alkanes Write the full mechanism of electrophilic addition of HX to an alkene Write the full mechanisms for SN1 and SN2 reactions Identify which alkyl halides undergo SN1 and SN2 reactions according to structure Identify and discuss the factors involved in facilitating SN1 and SN2 reactions Draw concise and detailed energy reaction diagrams for all reactions considered Reaction Mechanism What is a reaction mechanism? – – – – – – Overall description of the reaction Must include all reactants and products Which bonds are broken Which bonds are formed In which order Relative rates of steps (e.g. slow, fast) Bond Breaking There are two different ways in which bond breaking can happen: Homolytic cleavage – symmetrical breaking Heterolytic cleavage – asymmetrical breaking Remember that a single bond is made-up of two electrons Arrow conventions The arrow must begin at an electron-rich site (either fully negative or δ-) and move towards an electron-poor site (either fully positive or δ+) Bond breaking Homolytic cleavage – forms two free radicals Heterolytic cleavage – forms two ions Bond formation Homogenic bond formation Heterogenic bond formation Types of Reactions Free radical reactions – Homolytic bond breaking – Homogenic bond formation – Less common Polar reactions – Heterolytic bond breaking – Heterogenic bond formation – More common Free radical reactions A free radical has an odd number of electrons. It is missing an octet and is therefore very reactive There are two types of free radical reactions Free radical substitution Free radical addition Free radical addition A free radical seeking another electron to achieve stability causes the pi bond to break homolytically. This causes the free radical fragment (X) to connect onto one of the alkene carbons, while the other alkene carbon becomes a free radical site. Since a new free radical is formed, the reaction can continue until a reactant runs out. Ethylene polymerization Free radical addition chain reaction Free radical substitution Chlorination of methane Important industrial reaction Production of important organic solvents Mechanism 5-Minute Break Initiation Step A stable molecule is broken down to two free radicals This can be achieved by using UV light OR By using heat This is the slowest step in the process Propagation Steps Recognize these: a free radical attacks a stable molecule and produces another free radical and another stable molecule Faster – free radicals are reactive Chain reaction Most of the product is formed in propagation steps Propagation steps will stop when the limiting reactant runs out Termination Steps Recognize these: two free radicals react together Rare steps – free radicals are too reactive to build up their concentration significantly, thus very little product is formed through termination steps Electrophilic addition of HX The reaction intermediate is called a carbocation sp2 hybridized Trigonal planar geometry Empty 2p atomic orbital Reaction Energy Diagram Figure Explanations for Revision We see in the diagram above that the first activation energy is much higher than the second. Thus, the first step is slow and the second step is fast. Why is that? The first step involves the breaking of a pi bond, and this requires energy. The second step involves the attack of a fully negative particle (Br-) on the fully positive carbocation. Coulomb’s Law dictates that the large electrostatic attraction will make this step quite fast. We also see that the process is exergonic (negative ΔG) since the products lie below the reactants. This makes the process spontaneous. Markovnikov’s Rule Regiospecific reaction – atoms go in specific positions In electrophilic addition reactions of HX to an alkene, the H atom is captured by the alkene carbon having the most hydrogens, and the halogen atom is captured by the most highly substituted alkene carbon atom The SN2 Reaction S stands for Substitution N stands for Nucleophilic 2 stands for Bimolecular – Direct collision between two molecules – Rate Law → Rate = k[RX][Nu:-] – Second-order reaction – RX = alkyl halide – Nu:- = nucleophile (base) The SN2 Reaction Mechanism L – leaving group Nucleophile (Nu-) attacks the carbon that is connected to the leaving group – this is a collision-based reaction Transition state – trigonal bipyramidal geometry SN2 Reaction The Nucleophile must be able to attack the carbon centre There must be enough space for the attack to be effective If the carbon is attached to large groups, there is little space for the attack – steric hindrance SN2 and Steric Hindrance Does not work well for secondary and tertiary alkyl halides Above left, we have a tertiary alkyl halide. The attack site is obstructed by the methyl groups, and the nucleophile is not able to successfully attack, leading to a slow reaction. On the right, the attack site is clear, leading to a faster reaction SN2 Energy Diagram Figure Explanations for Revision This is a one-step reaction, with one activation energy, and one transition state. The nucleophile attacks the alkyl halide, leading to a trigonal bipyramidal transition state with partial chemical bonds. The Nu-C bond forms fully while the C-X bond breaks up completely, leading to the formation of the final product. 5-Minute Break Overall energy change Tertiary Alkyl Halide Tertiary alkyl halides cannot undergo substitution by SN2 mechanism YET The following substitution reaction does take place Conclusion: Different Mechanism! SN1 Reaction S stands for Substitution N stands for Nucleophilic 1 stands for Unimolecular Rate Law → Rate = k[RX] – Does not depend on the nucleophile concentration – First-order reaction SN1 Reaction Mechanism Step 1 – Bond breaks by itself – Slow Step 2 – Nucleophile attacks carbocation – Fast Figure Explanations for Revision The first step on the left involves the spontaneous breaking of the C-Br bond. This is difficult to achieve on its own and must be encouraged, for example, by using an appropriate polar solvent that will solvate the Br- ion when it detaches. Also, this step is further encouraged by having a stable carbocation with lower energy (leading to a lower activation energy for the first step). Tertiary carbocations are more stable, thus tertiary alkyl halides give faster reactions with this mechanism. Primary or methyl alkyl halides do not give fast reactions, and they prefer to react through an SN2 mechanism. Carbocation Stability A more stable carbocation means a faster Step 1 Methyl groups donate electron density to the positive C atom, reducing the total positive charge and making the carbocation more stable with lower energy and a lower activation energy (faster) Carbocation Stability Since a tertiary carbocation is most stable, the tertiary transition state is also at lower energy. This means a lower overall activation energy and a faster step SN1 Energy Diagram Figure Explanations for Revision It is noteworthy that the energy diagram for the SN1 reaction is very similar to the energy diagram for electrophilic addition of HX to an alkene. Two steps, with a slow first step and a faster second step. Both mechanisms involve the formation of an intermediate carbocation. Summary SN1 reaction – tertiary RX – Increase speed by increasing [RX] – Polar solvent – Large X group SN2 reaction – primary or methyl RX – Increase speed by increasing [RX] and [Nu] – Increase temperature (kinetic energy of collisions) Summary for Revision There are two principal types of organic reactions: free-radical reactions and polar reactions. The first involve the formation of free radicals (species with an odd number of electrons), whereas the second involve the formation of ions. Free radical reactions can be either free radical additions (polymerization), or free radical substitutions, usually leading to a mixture of products and therefore less useful from a synthetic point of view. Free radical substitution of CH4 with Cl2 involves three distinct steps: initiation, propagation, and termination. The mechanism of electrophilic addition of HX to an alkene involves two steps: a slow first step leading to the formation of an intermediate carbocation, and a faster second step with much lower activation energy. The energy diagram reflects these realities. SN2 nucleophilic substitution involves a collision-based mechanism whereby a nucleophile attacks an alkyl halide, kicking off the halogen atom and taking its place. This is a one-step reaction and this is reflected in the energy diagram having just one transition state and one activation energy. SN2 works well with methyl or primary alkyl halides. SN1 nucleophilic substitution involves a two-step mechanism with a slow first step and a faster second step. The energy diagram is very similar to that of electrophilic addition of HX to an alkene. SN1 works best with tertiary alkyl halides.