Organic chemistry for medicine and biology students Chem 2311 Chapter 6

1. Organic chemistry for medicine and biology students Chem 2311 Chapter 6 Alkylhalides (Substitution and Elimination) By Prof. Dr. Adel M. Awadallah Islamic University of Gaza

2. Alkyl Halides (Substitution and Elimination) • alkyl halides = Halogenoalkanes = haloalkanes contain a halogen atom - fluorine, chlorine, bromine or iodine - attached to an alkyl • The different kinds of halogenoalkanes • Primary (1°) includes CH3Br • Secondary (2°) Tertiary (3°)

3. The polarity of the carbon-halogen bonds • Electro negativity values (Pauling scale) • C = 2.5, F = 4.0, Cl = 3.0, Br = 2.8, I = 2.5 • Strengths of various bonds (all values in kJ mol-1). • C-H = 413 • C-F = 467 (very polar, but very strong and difficult to break) • C-Cl = 346 • C-Br = 290 • C-I = 228 (non polar, but it is polarized in the reaction by any nucleophile) Rates of reaction: RCl < RBr < RI

4. Nucleophilic substitution in primary alkyl halides • NucleophilesA nucleophile is a species (an ion or a molecule) which is strongly attracted to a region of positive charge in something else. • Nucleophiles are either fully negative ions, or else have a strongly - charge somewhere on a molecule. Common nucleophiles are hydroxide ions, cyanide ions, water and ammonia. • Notice that each of these contains at least one lone pair of electrons, either on an atom carrying a full negative charge, or on a very electronegative atom carrying a substantial - charge.

5. SN2 reaction (Substitution Nucleophilic bimolecular)The reaction is a one step reaction

6. Energy Diagram for SN2 reaction

7. Nucleophilic substitution in tertiary alkylhalides • The reaction occurs in two steps

8. Energy Diagram for SN1 Reaction

9. Nucleophilic substitution in secondary alkylhalides The reaction occurs in both mechanisms depending on : • Nucleophile strength (increases SN2) • Solvent polarity (aprotic solvents increases SN2) • Strength of nucleophiles • A) Charged nucleophiles are stronger than neutral ones • OH- > H2O , EtO- > EtOH, NH2- > NH3 • B) Nucleophile strength increases by going to the left in a period, or down in a group of the periodic table • NH3 > H2O, NH2- > OH- (period) • H2S > H2O, SH- > OH- (group)

12. The reaction with hydroxide ions • Primary alkylhalides • Tertiary alkylhalides

13. The Reaction with water • Primary alkylhalides

14. Tertiary alkylhalides

15. Elimination Reactions • Elimination (dehydrohalogenation) reactions of alkyl halides • A hydrogen atom and a halogen atom from adjacent carbons are eliminated and a carbon –carbon double bond is formed • Competition between substitution and elimination

16. Factors deciding substitution or elimination • 1) Type of alkylhalide • 2) The solvent • Water encourages substitution, • Ethanol encourages elimination. • 3) The temperature • Higher temperatures encourage elimination. • 4) Concentration of the sodium or potassium hydroxide solution • Higher concentrations favor elimination.

17. Mechanisms of Elimination1) E2 mechanism

18. Elimination from unsymmetric alkylhalides

19. 2) E1 Elimination

20. Elimination from unsymmetrical alkylhalides

21. Polyhalogenated aliphatic compounds • CH3Br (methyl bromide) • Methyl Bromide is a highly effective fumigant used to control a number of pests including insects • CH2Cl2 (dicholromethane or methylene chloride) • solvent • CHCl3 (Chloroform) • Solvent and was used as an anesthetic • (CF2-CF2)n Teflon • Chloroflouorocarbons (CFC) • CCl2F2 (Freon 12, CFC – 12) refrigerating gas

22. Halons • Bromine containing CFCsare called halons, and used to extinguish fire • CBrClF2 (Halon–1211) • CBrF3 (Halon-1301)