Alcohols and Others

• The most commonly occurring functional groups in organic chemistry are those that contains oxygen atom (C-O and C=O).
• Alcohols (R-OH) are characterized by the presence of a hydroxyl (-OH) group bonded to a carbon chain. Phenols (Ar-OH) have the -OH group attached to an aromatic ring.
• Ethers (R-O-R’) has an oxygen bonded to 2 carbons. Epoxides are ethers in a cyclic arrangement where the organic parts are also bonded to each other.
• Thiols (R-SH), Thiophenols (Ar-SH), and Sulfides (R-S-R’) are all analogs of the O-containing organic compounds.
• Alcohols, Phenols, and Ethers are seen as derivatives of water (H-O-H).
• ROH and Ar-OH exhibit H-bonding similar to H2O resulting to a higher boiling point than R-O-R’.
• ROH and Ar-OH are also weakly basic and weakly acidic like H2O.• As bases, they form oxonium ions.• As acids, they form alkoxide / phenoxide ions.
• Phenols are more acidic than alcohols.
• Despite the similarities, R-OH and Ar-OH undergoes different reactions.
• Ethers and Epoxides are both practically unreactive to most reagents which makes them good reaction solvents.
• R-SH and R-S-R’ are commonly found in living organisms. R-SH possess distinct appalling odor — skunk-like or rotten egg smell.
• Synthesis of Alcohols

  • Electrophilic Addition (Hydration)
  • Nucleophilic Substitution with haloalkanes
  • Carbonyl group via reduction
  • Carbonyl group via RMgX reaction
• Hydration

  alkene + H2O/H2SO4 (M) or BH3/THF (NM) -> Secondary Alcohol (M) or Primary Alcohol (NM)
• Nucleophilic Substitution

  RX + H2O -> Alcohol
• Reduction of carbonyl group uses compounds like aldehydes, ketones,carboxylic acids, and esters.
• Aldehydes and Ketones uses weak reducing agent — NaBH4 in wateror alcohol solution in a weakly acidic condition (H 3O+).• Aldehydes are reduced to 1° ROH and Ketones to 2° ROH.
• Carboxylic acid and Esters uses strong reducing agent — LiAlH4 inether solution in a weakly acidic condition (H 3O+).• Carboxylic acids and Esters are reduced to 1° ROH.
• Reduction of Carbonyl Group

  • NaBH4 and LiAlH4 adds a hydride ion to the carbonylcarbon resulting to an alkoxide intermediate.The intermediate is protonated by the acidic conditionfinally resulting to the alcohol product.
• Reduction or Carbonyl Group

  Aldehyde + NaBH4, ethanol/H3O+ = primary alcohol

  Ketone + NaBH4, ethanol/H3O+ = secondary alcohol

  Carboxylic Acid* + LiAlH4, ether/H3O+ = primary alcohol

  Ester** + LiAlH4, ether/H3O+ = primary alcohol

  * with H2O by-product

  ** with alcohol by-product
• Grignard reaction employs a reaction between Grignard reagent (RMgX) and carbonyl compounds like aldehydes, ketones, and esters.
• The RMgX adds a carbanion to the carbonyl carbon, similar toreduction adding a hydride, to produce various ROH products.• Formaldehyde with RMgX results to 1° ROH.• Aldehydes with RMgX results to 2° ROH.• Ketones and Esters with 2 RMgX results to 3° ROH.
• Grignard Reaction with Carbonyl Group

  Formaldehyde + RMgX, ether/H3O+ = primary alcohol

  Aldehyde + RMgX, ether/H3O+ = secondary alcohol

  Ketone + RMgX, ether/H3O+ = tertiary alcohol

  Ester* + 2RMgX, ether/H3O+ = tertiary alcohol

  * with alcohol by-product
• Reactions of Alcohol

  • Acid-catalyzed dehydration
  • Oxidation of Primary and Secondary Alcohol
  • Ether Synthesis
• Acid-catalyzed dehydration of ROH removes H2O from the ROH andforms an alkene product.• It follows an E1 mechanism with a carbocation intermediate and follows Zaitsev’s rule to determine the major product.• 2° and 3° ROH are dehydrated effectively in strong acid solution (eg.H2SO4/H2O)
• Acid-catalyzed Dehydration

  Alcohol + H2SO4/H2O -> Alkene
• Oxidation of alcohols is the most valuable reaction of ROH which produces carbonyl compounds (e.g aldehydes, ketones, carboxylic acids).
• ROH carrying alpha / benzylic hydrogens can undergo oxidation.• 1° ROH oxidizes into aldehyde then into a carboxylic acid.• 2° ROH oxidizes into a ketone.• 3° ROH do not undergo oxidation.
• Oxidation reagents: chromium trioxide (CrO3), Sodium dichromate (Na2Cr2O7), KMnO4 in acidic solution. The most common and current choice is periodinane in DCM.
• 1° and 2° ROH reacts with oxidizing agents toform aldehydes and ketones respectively.
• Aldehydes are intermediate in nature becausethe oxidization happens so fast it is convertedto carboxylic acid right away.
• 3° ROH do not react and cannot be oxidized. The non-reactivity of the 3° ROH to oxidizing agents is due the absence of alpha/benzylic hydrogens.
• Ether synthesis is a reaction that coverts R-OH to R-OR’ by reactingROH with RX via SN2 mechanism.• This reaction is called Williamson ether synthesis.• An alkali metal or a strong base like NaH reacts with ROH to form analkoxide (RO-).• The RO- reacts with 1° RX via SN2 mechanism.
• Williamson ether synthesis follows SN 2 mechanism. NaH aidsthe -OH to be a good leaving group and simultaneously thealkoxide (RO) ion substitutes the halogen from a 1° RX.In order to avoid E2 from happening, a bulkier alkoxide isused to react with a simpler (1°) RX.
• Ether Formation

  ROH + NaH -> Alkoxide ion + Haloalkane -> ether
• Synthesis of Phenol

  • Chlorination/Bromination
  • Sulfonation
• Phenols are aromatic alcohols that are synthesized via a special process called as the Dow Process.
• Dow Process can use substrates like a chlorobenzene or benzene sulfonic acid to react with NaOH to form a Na phenoxide which in turn will be set for pyrolysis. Upon acidification of the sodium phenoxide it yields the phenol product.
• Chlorination/Bromination for Phenol

  Benzene + Cl2 or Br2/FeCl3 or FeBr3 -> Chloro/bromobenzene + NaOH, H2O/350 heat C -> Na phenoxide + H+ -> Alcohol
• Sulfonation for Phenol

  Benzene + SO3/H2SO4 -> benzenesulfonic acid + NaOH/H2O -> NaOH/350 heat C -> Na phenoxide + H+ -> Alcohol
• Reactions of Phenols

  • Electrophilic Substitution
  • Williamson Ether Synthesis
  • Oxidation-Reduction