CHAPTER EIGHT Nucleophilic Substitution TABLE 8.3 Effect of Chain Branching on Reactivity of Primary Alkyl Alkyl bromide Structure Relative rate Ethyl bromide CHaCH.Br Propyl bromide Br sobutyl bromide (CH3)2 CHCH2 Br 0.036 Neopentyl bromide (CH3)3CCH2 Br 0.00002 Substitution of bromide by lithium iodide in acetone. Ratio of second-order rate constant k for indicated alkyl bromide to k for ethyl bromide at 25C. 8.7 NUCLEOPHILES AND NUCLEOPHILICITY The Lewis base that acts as the nucleophile often is, but need not always be, an anion Neutral Lewis bases can also serve as nucleophiles. Common examples of substitutions involving neutral nucleophiles include solvolysis reactions. Solvolysis reactions are sub- stitutions in which the nucleophile is the solvent in which the reaction is carried out. Solvolysis in water converts an alkyl halide to an alcohol Water Alkyloxonium halide halide Solvolysis in methyl alcohol converts an alkyl halide to an alkyl methyl ether: H3C、 H3C、 R+ⅹ-- HX H Methyl alcohol Dialkyloxonium halide In these and related solvolyses, the first stage is the one in which nucleophilic substitution takes place and is rate-determining. The proton-transfer step that follows it is much faster. Since, as we have seen, the nucleophile attacks the substrate in the rate determining step of the SN2 mechanism, it follows that the rate at which substitution occurs may vary from nucleophile to nucleophile. Just as some alkyl halides are more reactive than others, some nucleophiles are more reactive than others. Nucleophilic strength, or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate. By measuring the rate at which various Lewis bases react with methyl iodide in methanol, a list of their nucleophilicities relative to methanol as the standard nucleophile has been compiled. It is presented in Table 8.4 eutral Lewis bases such as water, alcohols, and carboxylic acids are much weaker nucleophiles than their conjugate bases. When comparing species that have the same nucleophilic atom, a negatively charged nucleophile is more reactive than a neutral one Back Forward Main MenuToc Study Guide ToC Student o MHHE Website8.7 NUCLEOPHILES AND NUCLEOPHILICITY The Lewis base that acts as the nucleophile often is, but need not always be, an anion. Neutral Lewis bases can also serve as nucleophiles. Common examples of substitutions involving neutral nucleophiles include solvolysis reactions. Solvolysis reactions are sub￾stitutions in which the nucleophile is the solvent in which the reaction is carried out. Solvolysis in water converts an alkyl halide to an alcohol. Solvolysis in methyl alcohol converts an alkyl halide to an alkyl methyl ether. In these and related solvolyses, the first stage is the one in which nucleophilic substitution takes place and is rate-determining. The proton-transfer step that follows it is much faster. Since, as we have seen, the nucleophile attacks the substrate in the rate￾determining step of the SN2 mechanism, it follows that the rate at which substitution occurs may vary from nucleophile to nucleophile. Just as some alkyl halides are more reactive than others, some nucleophiles are more reactive than others. Nucleophilic strength, or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate. By measuring the rate at which various Lewis bases react with methyl iodide in methanol, a list of their nucleophilicities relative to methanol as the standard nucleophile has been compiled. It is presented in Table 8.4. Neutral Lewis bases such as water, alcohols, and carboxylic acids are much weaker nucleophiles than their conjugate bases. When comparing species that have the same nucleophilic atom, a negatively charged nucleophile is more reactive than a neutral one. Methyl alcohol O H3C H Alkyl halide R X slow fast Dialkyloxonium halide O H3C H R X Alkyl methyl ether ROCH3 Hydrogen halide HX Water O H H Alkyl halide R X slow fast Alkyloxonium halide O H H R X Alcohol ROH Hydrogen halide HX 312 CHAPTER EIGHT Nucleophilic Substitution TABLE 8.3 Effect of Chain Branching on Reactivity of Primary Alkyl Bromides Toward Substitution Under SN2 Conditions* Alkyl bromide Ethyl bromide Propyl bromide Isobutyl bromide Neopentyl bromide CH3CH2Br CH3CH2CH2Br (CH3)2CHCH2Br (CH3)3CCH2Br Structure 1.0 0.8 0.036 0.00002 Relative rate† *Substitution of bromide by lithium iodide in acetone. † Ratio of second-order rate constant k for indicated alkyl bromide to k for ethyl bromide at 25°C. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website