CHAPTER EIGHT Nucleophilic Substitution Increasing rate of substitution RF RCI RB Least reactive Most reactive The order of alkyl halide reactivity in nucleophilic substitutions is the same as their order in eliminations. lodine has the weakest bond to carbon and iodide is the best leavin group. Alkyl iodides are several times more reactive than alkyl bromides and from 50 to 100 times more reactive than alkyl chlorides. Fluorine has the strongest bond to car bon, and fluoride is the poorest leaving group. Alkyl fluorides are rarely used as sub- strates in nucleophilic substitution because they are several thousand times less reactive han alkyl chlorides propane was allowed to react with one molar equivalent of sodium cyanide:o. PROBLEM 8.2 A single organic product was obtained when 1-bromo-3-chlor aqueous ethanol. What was this product? Leaving-group ability is also related to basicity. A strongly basic anion is usually aving group ability and ba. a poorer leaving group than a weakly basic one. Fluoride is the most basic and the poor sicity is explored in more de. est leaving group among the halide anions, iodide the least basic and the best leav 8.3 THE SN2 MECHANISM OF NUCLEOPHILIC SUBSTITUTION The mechanisms by which nucleophilic substitution takes place have been the subject of much study. Extensive research by Sir Christopher Ingold and Edward D. Hughes and their associates at University College, London, during the 1930s emphasized kinetic and eochemical measurements to probe the te mechanisms of these reactions Recall that the term kinetics" refers to how the rate of a reaction varies wi changes in concentration. Consider the nucleophilic substitution in which sodium hydrox ide reacts with methyl bromide to form methyl alcohol and sodium bromide →>CH3OH+Br Methyl bromide Hydroxide ion Methyl alcohol Bromide ion The rate of this reaction is observed to be directly proportional to the concentration of both methyl bromide and sodium hydroxide. It is first-order in each reactant, or second Rate= k[Ch3 Br[HO I Hughes and Ingold interpreted second-order kinetic behavior to mean that the rate determining step is bimolecular that is, that both hydroxide ion and methyl bromide involved at the transition state. The symbol given to the detailed description of the mech- The Sn2 mechanism was in anism that they developed is SN2, standing for substitution nucleophilic bimolecular. The Hughes and Ingold SN2 mechanism is a single-step process in which both the 4.13 alkyl halide and the nucleophile are involved at the transition state. Cleavage of the bond between carbon and the leaving group is assisted by formation of a bond between car bon and the nucleophile. In effect, the nucleophile "pushes off" the leaving group from Back Forward Main MenuToc Study Guide ToC Student o MHHE WebsiteThe order of alkyl halide reactivity in nucleophilic substitutions is the same as their order in eliminations. Iodine has the weakest bond to carbon, and iodide is the best leaving group. Alkyl iodides are several times more reactive than alkyl bromides and from 50 to 100 times more reactive than alkyl chlorides. Fluorine has the strongest bond to car￾bon, and fluoride is the poorest leaving group. Alkyl fluorides are rarely used as sub￾strates in nucleophilic substitution because they are several thousand times less reactive than alkyl chlorides. PROBLEM 8.2 A single organic product was obtained when 1-bromo-3-chloro￾propane was allowed to react with one molar equivalent of sodium cyanide in aqueous ethanol. What was this product? Leaving-group ability is also related to basicity. A strongly basic anion is usually a poorer leaving group than a weakly basic one. Fluoride is the most basic and the poor￾est leaving group among the halide anions, iodide the least basic and the best leaving group. 8.3 THE SN2 MECHANISM OF NUCLEOPHILIC SUBSTITUTION The mechanisms by which nucleophilic substitution takes place have been the subject of much study. Extensive research by Sir Christopher Ingold and Edward D. Hughes and their associates at University College, London, during the 1930s emphasized kinetic and stereochemical measurements to probe the mechanisms of these reactions. Recall that the term “kinetics” refers to how the rate of a reaction varies with changes in concentration. Consider the nucleophilic substitution in which sodium hydrox￾ide reacts with methyl bromide to form methyl alcohol and sodium bromide: The rate of this reaction is observed to be directly proportional to the concentration of both methyl bromide and sodium hydroxide. It is first-order in each reactant, or second￾order overall. Rate  k[CH3Br][HO] Hughes and Ingold interpreted second-order kinetic behavior to mean that the rate￾determining step is bimolecular, that is, that both hydroxide ion and methyl bromide are involved at the transition state. The symbol given to the detailed description of the mech￾anism that they developed is SN2, standing for substitution nucleophilic bimolecular. The Hughes and Ingold SN2 mechanism is a single-step process in which both the alkyl halide and the nucleophile are involved at the transition state. Cleavage of the bond between carbon and the leaving group is assisted by formation of a bond between car￾bon and the nucleophile. In effect, the nucleophile “pushes off” the leaving group from Methyl bromide CH3Br Hydroxide ion HO Bromide ion Br Methyl alcohol CH3OH Increasing rate of substitution by nucleophiles RF  RCl  RBr  RI Least reactive Most reactive 306 CHAPTER EIGHT Nucleophilic Substitution The relationship between leaving group ability and ba￾sicity is explored in more de￾tail in Section 8.14. The SN2 mechanism was in￾troduced earlier in Section 4.13. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website