CHAPTER EIGHT Nucleophilic Substitution FIGURE 8.1 Two contrasting ubstitution of a leaving group(red) by a nucleophile blue). In(a)the nucleophile attacks carbon at the same side from which the leaving group departs In(b)nucle ophilic attack occurs at the (a) Nucleophilic substitution with retention of configuration side opposite the bond to the leaving group. (b)Nucleophilic substitution with inversion of configuration Nucleophilic substitution had occurred with inversion of configuration, consistent with the following transition state CH3(CH,)s H HO PROBLEM 8.4 The Fischer projection formula for (+)-2-bromooctane is shown For a ch Write the Fischer projection of the (-)-2-octanol formed from it by nucleophilic with molecu. substitution with inversion of configuration structura H CH2( CH2)4CH3 PROBLEM 8.5 Would you expect the 2-octanol formed by sn2 hydrolysis of (-) tion and sign of rotation? What about the 2-octanol formed by hydrolysis of racemic 2-brom Numerous similar experiments have demonstrated the generality of this observation. Substitution by the SN2 mechanism is stereospecific and proceeds with inversion of con The first example of a stereo. figuration at the carbon that bears the leaving group. There is a stereoelectronic require- electronic effect in this text ment for the nucleophile to approach carbon from the side opposite the bond to the leav. concerned anti elimination ing group. Organic chemists often speak of this as a Walden inversion, after the German E2 reactions of alkyl halides(Section 5. 16) heist Paul Walden, who described the earliest experiments in this area in the 1890 8.5 HOW SN2 REACTIONS OCCUR When we consider the overall reaction stereochemistry along with the kinetic data, a fairly complete picture of the bonding changes that take place during SN2 reactions merges. The potential energy diagram of Figure 8.2 for the hydrolysis of (S)-(+)-2- ctane is one that is consistent with the experimental observations Back Forward Main MenuToc Study Guide ToC Student o MHHE WebsiteNucleophilic substitution had occurred with inversion of configuration, consistent with the following transition state: PROBLEM 8.4 The Fischer projection formula for ()-2-bromooctane is shown. Write the Fischer projection of the ()-2-octanol formed from it by nucleophilic substitution with inversion of configuration. PROBLEM 8.5 Would you expect the 2-octanol formed by SN2 hydrolysis of ()- 2-bromooctane to be optically active? If so, what will be its absolute configura￾tion and sign of rotation? What about the 2-octanol formed by hydrolysis of racemic 2-bromooctane? Numerous similar experiments have demonstrated the generality of this observation. Substitution by the SN2 mechanism is stereospecific and proceeds with inversion of con- figuration at the carbon that bears the leaving group. There is a stereoelectronic require￾ment for the nucleophile to approach carbon from the side opposite the bond to the leav￾ing group. Organic chemists often speak of this as a Walden inversion, after the German chemist Paul Walden, who described the earliest experiments in this area in the 1890s. 8.5 HOW SN2 REACTIONS OCCUR When we consider the overall reaction stereochemistry along with the kinetic data, a fairly complete picture of the bonding changes that take place during SN2 reactions emerges. The potential energy diagram of Figure 8.2 for the hydrolysis of (S)-()-2- bromooctane is one that is consistent with the experimental observations. CH3 H Br CH2(CH2)4CH3 C CH3(CH2)5 H HO Br CH3   308 CHAPTER EIGHT Nucleophilic Substitution

(a) Nucleophilic substitution with retention of configuration

(b) Nucleophilic substitution with inversion of configuration The first example of a stereo￾electronic effect in this text concerned anti elimination in E2 reactions of alkyl halides (Section 5.16). For a change of pace, try doing Problem 8.4 with molecu￾lar models instead of making structural drawings. FIGURE 8.1 Two contrasting stereochemical pathways for substitution of a leaving group (red) by a nucleophile (blue). In (a) the nucleophile attacks carbon at the same side from which the leaving group departs. In (b) nucle￾ophilic attack occurs at the side opposite the bond to the leaving group. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website