Alkyl Halides Part 2 PDF

Alkyl Halides Organic chemistry Alkyl Halides To draw any nucleophilic substitution product: Find the sp3 hybridized carbon with the leaving group. Identify the nucleophile, the species with a lone pair or π bond. Substitute the nucleophile for the leaving group and assign charges (if necessary) to...

Alkyl Halides Organic chemistry Alkyl Halides To draw any nucleophilic substitution product: Find the sp3 hybridized carbon with the leaving group. Identify the nucleophile, the species with a lone pair or π bond. Substitute the nucleophile for the leaving group and assign charges (if necessary) to any atom that is involved in bond breaking or bond formation. Alkyl Halides Drawing Products of Nucleophilic Substitution Reactions The overall effect of any nucleophilic substitution is the replacement of the leaving group by the nucleophile. Alkyl Halides Nucleophiles in Substitution Reactions Nucleophiles are Lewis bases that can be negatively charged or neutral. Negatively charged nucleophiles like HOˉ and HSˉ are used as salts with Li+, Na+, or K+ counter ions to balance the charge. Since the identity of the counter ion is usually inconsequential, it is often omitted from the chemical equation. Alkyl Halides Nucleophiles in Substitution Reactions: The Leaving Group In a nucleophilic substitution reaction of R-X, the C-X bond is heterolytically cleaved, and the leaving group departs with the electron pair in that bond, forming X:¯. The more stable the leaving group X:¯, the better able it is to accept an electron pair. For example, H2O is a better leaving group than HO¯ because H2O is a weaker base. Alkyl Halides Trends in Leaving Group Ability The weaker the base, the better the leaving group. Alkyl Halides Good Leaving Groups Alkyl Halides Poor Leaving Groups Alkyl Halides Nucleophiles and Bases Nucleophiles and bases are structurally similar: both have a lone pair or a π bond. They differ in what they attack. Bases attack protons. Nucleophiles attack other electron-deficient atoms (usually carbons). Alkyl Halides Nucleophilicity Parallels Basicity Nucleophilicity parallels basicity in three instances: 1. For two nucleophiles with the same nucleophilic atom, the stronger base is the stronger nucleophile. The relative nucleophilicity of HO¯ and CH3COO¯, is determined by comparing the pKa values of their conjugate acids (H2O = 15.7, and CH3COOH = 4.8). HO¯ is a stronger base and stronger nucleophile than CH3COO¯. Alkyl Halides Nucleophilicity Parallels Basicity 2. A negatively charged nucleophile is always a stronger nucleophile than its conjugate acid. HO¯ is a stronger base and stronger nucleophile than H2O. 3. Right-to-left across a row of the periodic table, nucleophilicity increases as basicity increases: Alkyl Halides Steric Effects on Nucleophile Strength Nucleophilicity does not parallel basicity when steric hindrance becomes important. Steric hindrance is a decrease in reactivity resulting from the presence of bulky groups at the site of a reaction. Steric hindrance decreases nucleophilicity but not basicity. Sterically hindered bases that are poor nucleophiles are called nonnucleophilic bases. Alkyl Halides Steric Effects on Nucleophile Strength Alkyl Halides Bond Breaking & Making in Nucleophilic Substitution Mechanisms But what is the order of bond making and bond breaking? In theory, there are three possibilities: Bond making and breaking occur at the same time. Bond breaking occurs first. Bond making occurs first. Alkyl Halides Nucleophilic Substitution Mechanisms–Concerted 1.Bond making and bond breaking occur at the same time. The mechanism is comprised of one step. In such a bimolecular reaction, the rate depends upon the concentration of both reactants. The rate equation is second order. Alkyl Halides Nucleophilic Substitution Mechanisms– Bond Breaking First 2. Bond breaking occurs before bond making. The mechanism has two steps and a carbocation is formed as an intermediate. The first step is rate-determining. The rate depends on the concentration of RX only. The rate equation is first order. Alkyl Halides Nucleophilic Substitution Mechanisms– Bond Making First 3. Bond making occurs before bond breaking. This mechanism has an inherent problem. The intermediate generated in the first step has 10 electrons around carbon, violating the octet rule. Because two other mechanistic possibilities do not violate a fundamental rule, this last possibility can be disregarded. Alkyl Halides Kinetics and Mechanisms Consider reaction 1: Kinetic data show that the rate of reaction1 depends on the concentration of both reactants, which suggests a bimolecular reaction with a one-step mechanism. This is an example of an SN2 (substitution nucleophilic bimolecular) mechanism. Alkyl Halides Inversion in SN2 Reactions Two examples showing inversion of configuration at a stereogenic center. Alkyl Halides Substrate Reactivity in SN2 Reactions As the number of R groups on the carbon with the leaving group increases, the rate of an SN2 reaction decreases. Methyl and 1° alkyl halides undergo SN2 reactions with ease. 2° Alkyl halides react more slowly. 3° Alkyl halides do not undergo SN2 reactions due to steric effects. Bulky R groups near the reaction site make nucleophilic attack from the backside more difficult, slowing the reaction rate. Alkyl Halides Characteristics of the SN2 Mechanism Alkyl Halides SN1 reaction mechanism The mechanism of an SN1 reaction would be drawn as follows: Note the curved arrow formalism that is used to show the flow of electrons. Key features of the SN1 mechanism are that it has two steps, and carbocations are formed as reactive intermediates. Alkyl Halides SN1 Kinetics SN1 reactions exhibit 1st order kinetics. The reaction is unimolecular – involving only the alkyl halide. The identity and concentration of the nucleophile have no effect on the reaction rate. Therefore, the nucleophile does not appear in the rate equation. rate = k[R3CBr] Alkyl Halides Racemization in SN1 Reactions Loss of the leaving group in Step generates a planar carbocation that is achiral. In Step , attack of the nucleophile can occur on either side to afford two products which are a pair of enantiomers. Because there is no preference for nucleophilic attack from either direction, an equal amount of the two enantiomers is formed—a racemic mixture. This process is called racemization. Alkyl Halides Racemization in SN1 Reactions Alkyl Halides Examples