Alkyl halides, Alcohols, Ethers, Thiols

1. Alkyl halides, Alcohols, Ethers, Thiols

2. Required background: Acidity and basicity Functional groups Molecular geometry and polarity Essential for: 1. Chemistry of carbonyl compounds 2. Reactions under basic conditions 3. Chemistry of acetals and ketals

3. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

5. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

6. 1. Addition of Hal2 or HHal to alkenes (see unit “Alkenes”) 2. Radical halogenation of alkanes a. Chain initiation Cl2 = 2Cl. (requires irradiation by light or high temperatures) b. Chain propagation RH + Cl. = R. + HCl; R. + Cl2 = RCl + Cl. c. Chain termination 2Cl. = Cl2; 2R. = R2; R. + Cl. = RCl Br2 reacts like Cl2, but it is less reactive and more selective. I2 does not react this way, because I. is too stable to split the C-H bond. F2 is so reactive that it breaks both C-H and C-C bonds: 7F2 + C2H6 = 2CF4 + 6HF

7. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

9. The SN1 mechanism takes place: 1. For tertiary substrates – always 2. For secondary substrates – sometimes 3. For primary substrates - never

10. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

11. V = k[substrate][Nu-] The SN2 mechanism takes place: 1. For tertiary substrates – never 2. For secondary substrates – sometimes 3. For primary substrates - always

13. Nucleophilicity is the ability to donate a pair of electrons at the moment of nucleophilic substitution. Nucleophilicity depends on the ability of the nucleophile to donate a pair of electrons to H+ (basicity) and on the influence on such ability from the substrate (usually polarizability). Polarizability is characteristic for large atoms and greatly increases nucleophilicity. Weaker bases make better leaving groups.

15. How to improve the leaving group? Make it neutral (decrease its basicity)

18. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

19. Regioselectivity of E2 Reminder: Alkoxides are stronger bases, than OH- due to weaker solvation This is another example of the Zaitsev’s rule.

21. Nucleophilicity and basicity of Y- do not affect the reactions E1 and SN1, because Y- is not involved in the rate limiting step.

22. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

23. Chloroform (CHCl3) and dichloromethane (CH2Cl2) are non-flammable organic solvents Tetrachloroethylene, trichloroethylene are dry-cleaning solvents Herbicides and pesticides: Refrigerants (chlorofluorohydrocarbons)

26. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

27. In a polar solution, acidity of alcohols is lower, than acidity of water due to the lessefficient solvation of the alkoxides (steric reason).

28. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

29. Zaitsev’s rule: During elimination hydrogen is eliminated from the least hydrogenated carbon The Zaitsev’s rule controls regioselectivity of elimination and based on different stability of transition states with partial double bonds

30. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry

34. Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. SN1 reaction 4. SN2 reaction 5. E1, E2 reactions 6. Applications of alkyl halides 7. Acidity and basicity of alcohols 8. Dehydration of alcohols 9. Synthesis of ethers 10. Solvents in organic chemistry