Alkyl halides, Alcohols, Ethers, Thiols

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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

1. Addition of Hal 2 or HHal to alkenes (see unit “Alkenes”) 2. Radical halogenation of alkanes a. Chain initiation Cl 2 = 2Cl. (requires irradiation by light or high temperatures) b. Chain propagation RH + Cl. = R. + HCl; R. + Cl 2 = RCl + Cl. c. Chain termination 2Cl. = Cl 2 ; 2R. = R 2 ; R. + Cl. = RCl Br 2 reacts like Cl 2, but it is less reactive and more selective. I 2 does not react this way, because I. is too stable to split the C-H bond. F 2 is so reactive that it breaks both C-H and C-C bonds: 7F 2 + C 2 H 6 = 2CF 4 + 6HF

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

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

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.

FactorSN1SN1SN2SN2 Stability of carbocation +No effect Steric hindrance No effect- Nucleophilicity No effect+ Good leaving group ++

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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

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

Nucleophilicity and basicity of Y - do not affect the reactions E1 and S N 1, because Y - is not involved in the rate limiting step.

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

Chloroform (CHCl 3 ) and dichloromethane (CH 2 Cl 2 ) are non-flammable organic solvents Tetrachloroethylene, trichloroethylene are dry-cleaning solvents Herbicides and pesticides: Refrigerants (chlorofluorohydrocarbons)

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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

Outline 1. Structures of alkyl halides, alcohols, and ethers 2. Synthesis of alkyl halides 3. S N 1 reaction 4. S N 2 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