Organic Chemistry Chapter 8 Alcohols, Phenols, and Ethers

Summary of Reactions to/from Alcohols, Phenols, and Ethers 1. Synthesis (a)Reduction of aldehydes to give primary alcohol (b)Reduction of ketones to give secondary alcohol (c)Reduction of esters to give primary alcohol (d)Reduction of carboxylic acids to give primary alcohol 2. Reaction of alcohols (a)Dehydration to give alkenes (b)Oxidation to give carbonyl compounds (c)Conversion into ethers 3. Synthesis of phenols 4. Synthesis of ethers (a)Wiliamson ether synthesis (b)Epoxides

Summary of Reactions to/from Alcohols, Phenols, and Ethers 5. Reaction of ethers (a)Acidic cleavage with HBr or HI (b)Epoxides cleavage with aqueous acids 6. Synthesis of thiols 7. Synthesis of disulfides

Nomenclature Alcohols, Phenols, and Ethers Nomenclature Nomenclature of Alcohols Step 1: Find the longest chain with OH / Replace the parent ending –e With –ol Step 2: Number the parent, beginning at the end nearer the OH Step 3: Number all substituents. Phenols Parent name as “-phenol” Designate the number and name of the substituents Ethers Simple ether without other substituents: Substituent1 substituent2 ether If large functional group (substituents) Alkoxy functional group

Nomenclature Alcohols, Phenols, and Ethers Nomenclature

All about alcohols ?

Properties of alcohols, ethers, phenols BPs of alcohols: are far higher than alkyl halide and alkanes with the same # of carbon = Because of hydrogen bonding Alcohols and Phenols as acid and base

Synthesis of alcohols 1.Hydration of alkenes 2.Reduction of carbonyl compounds

Synthesis of Alcohols: Reduction of Carbonyls 1.Reduction of aldehydes/ketones 2.Reduction of esters and carboxylic acids

Reagents and Hydrogen Sources in Reductive Synthesis Synthesis Reducing reagents: NaBH 4 for aldehyde and ketones LiAlH 4 for carboxylic acid and ester

Notice the reactivity of reducing reagents Selective Reduction to Alcohols or Esters NaBH 4 : Mild, only for ketone and aldehyde LiAlH 4 : Nearly all carbonyls

Reactions of Alcohols 1.Dehydration of alcohol: Acid-catalyzed reaction

Reactions of Alcohols 1.Dehydration of alcohol: Acid-catalyzed reaction Note: Zaitsev’s rule following and E1 mechanism

Reactions of Alcohols 2. Oxidation of alcohol: Production of carbonyls Alcohols  Aldehydes  Carboxylic acids Alcohols  Ketones

Reactions of Alcohols 2. Oxidation of alcohol: Production of carbonyls Common oxidizing reagent: PCC: Alcohol to aldehyde CrO 3, Na 2 Cr 2 O 7 : Alcohol to carboxylic acid or Ketone or Ketone

Reactions of Alcohols 3. Conversion into ethers (Williamson ether syn.)

Reagent pairs of Williamson Ether Synthesis Williamson Ether Synthesis: Reaction between Alkoxide and Alkyl halide S N 2 mechanism following / Competing E2 reaction Best option for ether: Hindered Alkoxide + Less Hindered Alkyl Halide

Synthesis of Phenols 1.Sulfonation-Desulfonation of Aromatic Ring

Reactions of Phenols 1.Alcohol-like reactions of phenols (Ether synthesis) Similarity/difference between alcohol / phenol: Ether formation: same reaction mechanism but dehydration/RX formation with HX (Not possible)

Reactions of Phenols 2. Electrophilic Aromatic Substitution of Phenols OH in Aromatic ring: o- and p-directing and activating

Reactions of Phenols 3. Oxidation of Phenols: Hydroquinone vs Quinone Quinone-hydroquinone interconversion: One of the most important reaction in biochemical reaction

Reactions of Phenols 3. Oxidation of Phenols: Hydroquinone vs Quinone Quinone-hydroquinone interconversion: Redox of Ubiquinone/hydroquinone as part of respiration

Reactions of Phenols 3. Quinone-hydroquinone interconversion: One of the most important reaction in biochemical reaction

Synthesis and Reaction of Ethers 1.Synthesis: Williamson Ether Synthesis (as described) 2.Reaction: - In most cases, ethers are pretty stable - But return to alcohol by strong mineral acid (HI and HBr) Where does the oxygen go ? - Ether with less hindered pair: more hindered, S N 2 - Ether with tertiary alkyl: less hindered, S N 1

EpoxidesEpoxides Epoxide as cyclic ether but much more reactive Epoxide (oxirane) is three membered oxygen heterocycle Synthesis: Alkene/Aromatics with Peracid Reactions: Cleavage to diol under acidic condition

Epoxides as Mutagenic Compounds Polycyclic aromatic hydrocarbon (e.g., benzo[a]pyrene) are potent Mutagens through : 1) Metabolic conversion to epoxide by cytochrome P450 2) Followed by reaction of amine from DNA base to adduct

Thiols and Sulfides Thiols: The most notorious unforgettable smells

Thiols and Sulfides Thiols: Analogues of alcohol with –SH rather than –OH Sulfide: Analogues of ether with R-S-R’, rather than R-O-R’ Nomenclature: Thiols: parent + thiol (rather than –ol) Sulfide: Substituent1 substituent2 + sulfideSynthesis