1. 7 7-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

2. 7 7-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Alkyl Halides Chapter 7

3. 7 7-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure Alkyl halide:Alkyl halide: a compound containing a halogen atom covalently bonded to an sp 3 hybridized carbon atom given the symbol RX

4. 7 7-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Vinylic and Aryl Halides if the halogen is bonded to an sp 2 hybridized carbon, the compound is called a vinylic halide if the halogen is bonded to a benzene ring, it is called an aryl halide, given the symbol Ar-X we do not study vinylic and aryl halides in this chapter

5. 7 7-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature locate the parent alkane number the parent chain to give the substituent encountered first, be it halogen or an alkyl group, the lower number halogen substituents are indicated by the prefixes fluoro-, chloro-, bromo-, and iodo- and listed in alphabetical order with other substituents

6. 7 7-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature for haloalkenes, numbering is determined by the location of the C-C double bond

7. 7 7-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature common names - name the alkyl group followed by the name of the halide

8. 7 7-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature several polyhaloalkanes are common solvents and are generally referred to by their common or trivial names

9. 7 7-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Freons & Their Alternatives The Freons are chlorofluorocarbons (CFCs). Among the most widely used are/were Nonozone-depleting alternatives are hydrofluorocarbons (HFCs) and hydrochlorofluorocarbons (HCFCs) including

10. 7 7-10 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nucleophilic Substitution Nucleophilic substitutionNucleophilic substitution: any reaction in which one nucleophile is substituted for another NucleophileNucleophile: a molecule or ion that donates a pair of electrons to another molecule or ion to form a new covalent bond: a Lewis base

11. 7 7-11 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nucleophilic Substitution One of the most important reactions of alkyl halides

12. 7 7-12 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nucleophilic Substitution

13. 7 7-13 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanisms Chemists propose two limiting mechanisms for nucleophilic aliphatic substitution a fundamental difference between them is the timing of bond-breaking and bond-forming steps they are designated S N 1 and S N 2

14. 7 7-14 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 2 Bond breaking and bond forming occur simultaneously S = substitution N = nucleophilic 2 = bimolecular Bimolecular reactionBimolecular reaction: a reaction in which two reactants are involved in the transition state of the rate-limiting step

15. 7 7-15 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 2 Simultaneous backside attack of the nucleophile and departure of the leaving group

16. 7 7-16 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 1 Bond breaking is complete before bond forming begins S = substitution N = nucleophilic 1 = unimolecular Unimolecular reactionUnimolecular reaction: a reaction in which only one species is involved in the transition state of the rate-limiting step

17. 7 7-17 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 1 An S N 1 mechanism is illustrated by the reaction of 2-bromo-2-methylpropane (tert-butyl bromide) and methanol

18. 7 7-18 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 1 Step 1: ionization of the C-X bond to form a carbocation intermediate

19. 7 7-19 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 1 Step 2: reaction of the carbocation (a Lewis acid) with methanol (a Lewis base) to form an oxonium ion

20. 7 7-20 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Mechanism - S N 1 Step 3: proton transfer to solvent completes the reaction

21. 7 7-21 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Stereochemistry of S N 1 For an S N 1 reaction at a stereocenter, the product is a racemic mixture

22. 7 7-22 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Stereochemistry S N 1

23. 7 7-23 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Evidence of S N reactions What effect of does the structure of the nucleophile have on rate? the structure of alkyl halide have on rate? the structure of the leaving group have on rate? the solvent have on the reaction mechanism?

24. 7 7-24 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nucleophilicity NucleophilicityNucleophilicity: a kinetic property measured by the rate at which a Nu attacks a reference compound under a standard set of experimental conditions for example, the rate at which a set of nucleophiles displaces bromide ion from bromoethane in ethanol at 25°C Table 7.2 shows common nucleophiles and their relative nucleophilicities

25. 7 7-25 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nucleophilicity

26. 7 7-26 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure of RX electronic factorsS N 1 reactions are governed by electronic factors, namely the relative stabilities of carbocation intermediates 3° > 2° > 1° > methyl steric factorsS N 2 reactions are governed by steric factors, namely the relative ease of approach of the nucleophile to the site of reaction methyl > 1° > 2° > 3°

27. 7 7-27 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Structure of RX Reactivities for S N 1 and S N 2 are in opposite directions

28. 7 7-28 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. The Leaving Group The more stable the anion, the better the leaving ability the most stable anions are the conjugate bases of strong acids

29. 7 7-29 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Common Protic Solvents Protic solventProtic solvent: a solvent that contains an -OH group These solvents favor S N 1 reactions; the greater the polarity of the solvent, the easier it is to form carbocations in it

30. 7 7-30 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Common Aprotic Solvents Aprotic solventAprotic solvent:does not contain an -OH group it is more difficult to form carbocations in aprotic solvents these solvents favor S N 2 reactions

31. 7 7-31 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Summary of S N Rexns

32. 7 7-32 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Summary of S N Rexns

33. 7 7-33 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. S N 1/S N 2 Problems - 1 Predict the type of mechanism for this reaction, and the stereochemistry of the product

34. 7 7-34 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. S N 1/S N 2 Problems - 2 Predict the mechanism of this reaction

35. 7 7-35 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. S N 1/S N 2 Problems - 3 Predict the mechanism and the configuration of product

36. 7 7-36 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.  -Elimination  -Elimination  -Elimination: removal of atoms or groups of atoms from adjacent carbons to form a carbon- carbon double bond

37. 7 7-37 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.  -Elimination Example

38. 7 7-38 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.  -Elimination Zaitsev ruleZaitsev rule: the major product of a  -elimination is the more highly substituted alkene

39. 7 7-39 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.  -Elimination Example (follows Zaitsev rule)

40. 7 7-40 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.  -Elimination There are two limiting mechanisms for  - elimination reactions E1 mechanismE1 mechanism: breaking of the R-X bond is complete before reaction with base to break the C-H bond begins. Only R-X is involved in the rate-limiting step. E2 mechanismE2 mechanism: breaking of the R-X and C-H bonds is concerted. Both R-X and base are involved in the rate- limiting step.

41. 7 7-41 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. E1 Mechanism Step 1: rate-limiting ionization of the C-X bond to form a carbocation intermediate

42. 7 7-42 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. E1 Mechanism Step 2: proton transfer from the carbocation intermediate to the base (in this case, the solvent)

43. 7 7-43 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. E2 Mechanism A one-step mechanism; all bond-breaking and bond-forming steps are concerted

44. 7 7-44 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Summary of E1 versus E2

45. 7 7-45 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Summary of E1 versus E2

46. 7 7-46 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Alkyl Halides End Chapter 7