ORGANIC CHEMISTRY CHM 207

1. ORGANIC CHEMISTRY CHM 207 CHAPTER 5: ALKYL HALIDES NOR AKMALAZURA JANI

2. SUBTOPICS • Nomenclature and structures of alkyl halides. • Classification of alkyl halides. • Physical properties of alkyl halides. • Reaction of alkyl halides. 1) Formation of alkanes (Wurtz reaction) 2) Nucleophilic substitution reaction: i) Example: formation of alcohol, Williamson ether synthesis, amine synthesis, nitrile synthesis ii) Mechanism of nucleophilic substitution reactions. iii)Types of nucleophilic substitution reaction: SN1 and SN2 reaction.

3. 3) Elimination reaction (dehydrohalogenation of alkyl halides). - E1 and E2 reactions. • Uses of alkyl halides.

4. ALKYL HALIDES • General formula: CnH2n+1X where n = 1,2,… and X (halogen) • Functional group: halogen, -X (X = F, Cl, Br, I) • Naming alkyl halides: - same as nomenclature of alkanes

5. Classification of alkyl halides

6. PHYSICAL PROPERTIES • BOILING POINTS - molecules with higher molecular weight have higher boiling points. - reasons: the molecule is heavier, slower moving, have greater surface area, have larger London attractions, resulting higher boiling points. - example: CH3F CH3Cl CH3Br CH3I RMM 34 50.5 95 142 bp (°C) -78 -24 4 42

7. - compounds with branched have more spherical shapes, have smaller surface area, resulting lower boiling points. - alkyl halides with more carbon atoms have higher boiling points.

8. DENSITIES • - alkyl fluoride and alkyl chlorides (with one Cl atom) are • less dense than water. • - alkyl chloride with two or more chlorine atoms are denser than water. • - all alkyl bromides and alkyl iodides are denser than water.

9. REACTIONS OF ALKYL HALIDES

10. Formation of alkanes (Wurtz reaction) • Equation: 2R-X + 2Na → 2NaX + R-R • Example: 2CH3I + 2Na CH3-CH3 + 2NaI • Most suitable for preparation of higher alkanes containing an even number of carbon atoms. dry ether reflux

11. Alkanes containing an odd number of carbon atoms can be prepared by using a mixture of two different alkyl halides. • This reaction produces only low yields due to the formation of other alkanes as by-products. dry ether CH3I + 2Na + CH3CH2I CH3CH2CH3 + 2NaI + CH3CH2-CH2CH3 + CH3CH3 by-products

12. Reactions of alkyl halides • Two types of reactions: i) substitution reactions ii) elimination reactions

13. NUCLEOPHILIC SUBSTITUTION REACTIONS

16. Mechanism of nucleophilic substitution reactions δ- δ+ δ+ δ-

17. Type of nucleophilic substitution reactions: SN1 and SN2 reactions • S = substitution • N = nucleophilic • 1 = a first order (unimolecular) reaction • 2 = a second order (bimolecular) reaction

18. SN1 (Substitution, Nucleophilic, unimolecular) reactions • Unimolecular : only one molecule involved in the transition state of the rate-limiting step. • Example: the reaction between aqueous NaOH and tertiary alkyl halides.

19. The reaction is first order and the rate depends only on the concentration of the tertiary alkyl halides. Rate = k[(CH3)3CBr] • The concentration of OH- does not have any effect on the rate of reaction. • OH- does not involved in the rate-limiting step.

20. Carbocation rearrangement in SN1 reactions • Rearrangement of the carbon skeleton will take place if a more stable carbocation can be formed in the process. • For example, hydrolysis of the secondary alkyl bromide, 2-bromo-3-methylbutane, yields the tertiary alcohol, 2-methyl-2-butanol.

21. Reactivity towards SN1 substitution mechanisms follows the stability of carbocations: SN1 reactivity: 3o > 2o > 1o > CH3X retention inversion

22. SN2 (Substitution, Nucleophilic, bimolecular) reactions • The processes of bond breaking and bond forming occur simultaneously (one bond is forming, one bond is breaking). • The mechanism involves only one step. • For example, hydrolysis of iodomethane (primary alkyl halides) δ+ δ- δ- δ+ δ-

23. or • A second order reaction • Rate equation = k[CH3I][OH-] • Both iodomethane and the OH- are involved in the rate-limiting step. • SN2 reactivity:CH3 X >1o>2o>neopentyl > 3o • Factor that determines the order of reactivity in SN2 reactions is the steric effect. • A steric effect is one in which the rate of chemical reaction depends on the size or spatial arrangement of the groups attached to, or near to, the reaction site of the molecule.

24. Relative reactivities of primary, secondary, and tertiary alkyl halides • The reactivity of alkyl halides towards nucleophilic substitution depend on the halogen. • The rate of reaction decrease in the order R-I > R-Br > R-Cl > R-F (most reactive) (least reactive) • Reason: C-X bond become stronger from I to F

25. Comparison SN1 and SN2 reactions

26. Elimination reactions-dehydrohalogenation of alkyl halides • Elimination: loss of two atoms or groups from the substrate to form a pi bonds. • Dehydrohalogenation (removal of hydrogen and a halogen atom) of alkyl halide to form alkene.

27. The elimination reaction is occurred when the reaction used strong base for examples, t-butoxide ion ((CH3)3CO-) or OH- ion and heated at high temperature. • Dehydrohalogenation will yield an alkene that has the larger number of alkyl groups as the main product (Saytzeff’s rule). • Elimination reactions can be divided into two: i) E1 reaction ii) E2 reaction

28. E1(Elimination, unimolecular) reaction • The rate-limiting state involves a single molecular than a collision between two molecules. • A first order reaction. • Rate equation: k[RX] • E1 reactivity: Benzyl > allyl > 3o > 2o > 1o

30. E2(Elimination, bimolecular) reaction • A second order reaction. • Rate equation: k[RX][Base] • E2 reactivity: 3o > 2o > 1o • Mechanism:

31. Comparison E1 and E2 reactions

32. Alkyl halides Reactions Nu- 1O RCH2X RCH2Nu SN2 Nu- strong R2CHNu + alkene SN2 + E2 2O R2CHX B- (strong) alkene E2 Nu- (weak) R3CNu + alkene 3O SN1 + E1 R3CX B- (strong) alkene E2

33. SOME COMMON NUCLEOPHILES

34. USES OF ALKYL HALIDES • Solvents - industrial and household solvents. - carbon tetrachloride (CCl4) used for dry cleaning, spot removing. - methylene chloride (CH2Cl2) is used to dissolve the caffeine from coffee beans to produce decaffeinated coffee. • Reagents - as starting materials for making complex molecules. - for example, the conversion of alkyl halides to organometallic reagents (compounds containing carbon-metal bonds) is important tool for organic synthesis.

35. Anesthetics • - examples: chloroform (CHCl3) and ethyl chloride. • Freons: Refrigerants and foaming agents • - Freons (called chlorofluorocarbons, or CFCs) is used as a refrigerant gas. • Pesticides • - example: DDT (Dichloro Diphenyl-Trichloroethane) is used as insecticides.