1. Chapter 8 Nucleophilic Substitution

2. 8.1 Functional Group Transformation By Nucleophilic Substitution

3. Y : –RX Y R + + : X – nucleophile is a Lewis base (electron-pair donor) often negatively charged and used as Na + or K + salt substrate is usually an alkyl halide Nucleophilic Substitution

4. Substrate cannot be an a vinylic halide or an aryl halide, except under certain conditions to be discussed in Chapter 23. X CCX Nucleophilic Substitution

5. +RX gives an ether Alkoxide ion as the nucleophile.. O:O:O:O:.. R'– + : X R.. O..R' – Table 8.1 Examples of Nucleophilic Substitution

6. (CH 3 ) 2 CHCH 2 ONa + CH 3 CH 2 Br Isobutyl alcohol (CH 3 ) 2 CHCH 2 OCH 2 CH 3 + NaBr Ethyl isobutyl ether (66%) Example

7. +RX gives an ester Carboxylate ion as the nucleophile.. O:O:O:O:.. R'C – + : X R.. O.. R'C –O O Table 8.1 Examples of Nucleophilic Substitution

8. OK + CH 3 (CH 2 ) 16 C CH 3 CH 2 I acetone, water + KI O CH 2 CH 3 CH 3 (CH 2 ) 16 C Ethyl octadecanoate (95%) O OExample

9. +RX gives a thiol Hydrogen sulfide ion as the nucleophile.. S:S:S:S:.. H– + : X R.. S..H – Table 8.1 Examples of Nucleophilic Substitution

10. KSH + CH 3 CH(CH 2 ) 6 CH 3 Br ethanol, water + KBr + KBr 2-Nonanethiol (74%) CH 3 CH(CH 2 ) 6 CH 3 SH Example

11. +RX gives a nitrile Cyanide ion as the nucleophile – + : X R – C N:: C N: Table 8.1 Examples of Nucleophilic Substitution

12. DMSO Cyclopentyl cyanide (70%) Br NaCN+ CN + NaCN Example

13. +RX gives an alkyl azide Azide ion as the nucleophile + : X R –.. – N N N.. : : –+.. N N N.. :–+ Table 8.1 Examples of Nucleophilic Substitution

14. NaN 3 + CH 3 CH 2 CH 2 CH 2 CH 2 I 2-Propanol-water CH 3 CH 2 CH 2 CH 2 CH 2 N 3 + NaI Pentyl azide (52%) Example

15. +RX gives an alkyl iodide Iodide ion as the nucleophile + : X R – –.. : I.... : I..: Table 8.1 Examples of Nucleophilic Substitution

16. NaI is soluble in acetone; NaCl and NaBr are not soluble in acetone. acetone+NaI CH 3 CHCH 3 Br 63% +NaBr I Example

17. 8.2 Relative Reactivity of Halide Leaving Groups

18. RI RBr RCl RF most reactive least reactive Generalization Reactivity of halide leaving groups in nucleophilic substitution is the same as for elimination.

19. BrCH 2 CH 2 CH 2 Cl + NaCN A single organic product was obtained when 1-bromo-3-chloropropane was allowed to react with one molar equivalent of sodium cyanide in aqueous ethanol. What was this product? Br is a better leaving group than Cl Problem 8.2

20. BrCH 2 CH 2 CH 2 Cl + NaCN A single organic product was obtained when 1-bromo-3-chloropropane was allowed to react with one molar equivalent of sodium cyanide in aqueous ethanol. What was this product? CH 2 CH 2 CH 2 Cl + NaBr C N: Problem 8.2