1559r_eh06.099-11210/22/0520:19Page107 Solutions o Problems107 (b)()where the ou are asked it is necessary to devise two-in up of wo S2 reactions to get the prope stereochemic +Na+I-Acetone -H -H CH:O- H Na+-CN DMSO H -CN 一H (d)Does this ooThis showto which u are asked toh roup an alkylation reaction.This is just the same as an S2 reaction.but now appropriate haloalkane substrate to react with the nucleophile,instead of the other way around N CH,CH CH 42.(a))H0->CH,C02>H20 (2H0>CH,C02>H,0 (3)H0>CH:C02->H0 (b)(l)F->CI->Br->I- Larger size stabilizes negative charge,making base weake (2)1>Br->C>F galop6a (3)厂>Br>C>F Reverse order of (1).Solutions to Problems • 107 (b) In contrast to (a), where inversion of configuration at the stereocenter was required, you are asked here to substitute Br with CN with retention. Because each SN2 reaction proceeds with inversion, it is necessary to devise a two-inversion scheme made up of two SN2 reactions to get the proper stereochemical result. The first SN2 reaction must be done with a nucleophile that is also a good leaving group (I fits this description): (c) Notice that an inversion is required: In the substrate the Br is trans to the ring fusion hydrogens, whereas in the product the SCH3 group is cis to them. Use one SN2 reaction: (d) Does this look strange? This shows a nucleophile, to which you are asked to attach an alkyl group: an alkylation reaction. This is just the same as an SN2 reaction, but now you need to supply an appropriate haloalkane substrate to react with the nucleophile, instead of the other way around: 42. (a) (1) HO  CH3CO2  H2O (2) HO  CH3CO2  H2O (3) H2O  CH3CO2  HO (b) (1) F  Cl  Br  I (2) I  Br  Cl  F (3) I  Br  Cl  F Reverse order of (1). Larger size decreases solvation and increases polarizability, increasing nucleophilicity. Larger size stabilizes negative charge, making base weaker. Leaving-group ability is inversely related to basicity. For a single atom, nucleophilicity parallels basicity. Basicity increases with charge and decreases with charge stabilization. N CH3 CH3 CH3 N CH3I CH3CH2OH I Na Br SCH3 H H CH3OH SCH3 H H Second SN2 inversion Na CN CH3 CH3 H CN CH3O H DMSO CH3 CH3 First SN2 inversion Na I H Br H CH3O CH3 CH3 I H CH3O H Acetone 1559T_ch06_099-112 10/22/05 20:19 Page 107