Lecture 7: Alcohol Reactions Study Notes

Lecture 7: Alcohol Reactions

Learning Objectives

The key objectives of this lecture encompass multiple aspects of alcohol reactions which include:
1. Alcohol Synthesis Predictions:
- Predict the structure of alcohols prepared from various reactions based on given reagents and substrates, particularly focusing on the following types of reactions:
  a. Substitution
  b. Addition
  c. Reduction
  d. Grignard reagents
1. Protective Groups:
- Utilize protective groups for alcohols within synthetic pathways to prevent undesirable reactions.
1. Reactions Predication:
- Given reagents and an alcohol substrate, predict the structure and applicable stereochemistry for specific reactions, which include:
  a. Substitution
  b. Elimination
  c. Oxidation
1. Synthetic Pathways:
- Construct synthetic pathways that make effective use of alcohol reactions.

Preparations of Alcohols

Nucleophilic Substitution Reactions (SN1 or SN2):
- Alcohols can be produced via nucleophilic substitutions.
  - Example 1:
    - Determine the appropriate reagent needed for specified transformations (specific examples not fully detailed).
Addition Reactions of Alkenes and Alkynes:
- Alcohols can also be generated through addition reactions of alkenes and alkynes.
  - Example 2:
    - Fill in the missing reagents across specified reactions (examples require completion).
Reductions of Carbonyls:
- Converting carbonyl compounds can yield alcohols, achieved through various methods:
  - Catalytic Hydrogenation:
    - Example 3:
      - Complete the following reaction with respect to the addition of hydrogens:
        An acidic proton/hydrogen is defined as a hydrogen atom that donates a proton.
        A hydride ion is described as a hydrogen atom carrying a negative charge, seeking to add hydrogen (H) atoms to polar pi bonds.
        Note: This process requires high pressure and temperature conditions for reactions involving diatomic hydrogen ( $H_2$ ).

Reducing Agents for Alcohol Production

Sodium Borohydride (NaBH4) & Lithium Aluminum Hydride (LiAlH4):
- NaBH4:
  - Capable of reducing aldehydes and ketones only, excluding pi bonds, carboxylic acids, and esters.
- LiAlH4:
  - Broadly reduces aldehydes, ketones, carboxylic acids, and esters; however, it does not touch pi bonds.
- Grignard Reagents:
  - Useful for reducing aldehydes, ketones, and esters to produce alcohols by forming strong bases; they do not reduce carboxylic acids.

Protection of Alcohols

Alcohols possess very weak acidity.
Protective groups such as trimethylsilyl (TMS) can be utilized to protect alcohols during synthetic pathways.
- Example 4:
  - Complete specified transformations involving protected alcohols.

Reactions with Alcohols

Nucleophilic Substitutions:
- Alcohols can act as substrates in nucleophilic substitution reactions when they are combined with strong acids or Lewis acid catalysts like ZnCl2.
  - Example 5:
    - Complete the following mechanisms involving nucleophilic substitutions.
    - Tetrabutyl ammonium fluoride (TBAF) can be used as a reagent for transformations under specific conditions.
Conversion of Alcohols to Tosylates:
- Alcohols can be transformed into tosylates to provide more effective leaving groups during reactions.
Conversion to Alkyl Bromides and Alkyl Chlorides:
- Primary and secondary alcohols can be converted to corresponding alkyl bromides using phosphorus tribromide (PBr3) and to alkyl chlorides using thionyl chloride (SOCl2) in pyridine as a solvent.
  - Example 6:
    - Complete the provided reactions where alcohol is converted to these halides.

Eliminations Using Alcohols

Alcohols can act as substrates in elimination reactions.
- Example 7:
  - Complete specified elimination reactions in terms of alcohol substrates.
- E2 Mechanism:
  - Transform alcohols to better leaving groups before executing E2 reactions with a strong base.
  - Example 8:
    - Complete specified reactions utilizing the E2 mechanism.

Oxidation of Alcohols

Alcohols can be oxidized to form carbonyl compounds through various oxidizing agents:
- Common Oxidizing Agents:
 - Chromic Acid ( $H2CrO4$ ):
 - Produces toxic chromium by-products, which are challenging to dispose.
 - Pyridinium Chlorochromate (PCC):
 - Allows for controlled oxidation without dangerous by-products.
 - Swern Oxidation:
 - Uses ( $DMSO$ , ( $COCl2$ ), and $Et3N$ ); known for being more environmentally friendly compared to traditional agents as it does not produce chromium waste.
 - Conversions:
 - Primary alcohol converts to aldehyde; secondary alcohol can produce ketone.

Synthesis Using Alcohols

Example 9:
- Predict products for various reactions involving alcohol substrates.
Synthetic Pathways Formation:
- Example 10:
  - Devise synthetic pathways for given transformations including alcohols.
  - Specifics to be formulated based on the substrate and reagents in question.

Alcohol Synthesis Predictions:
- Nucleophilic Substitution (SN1 or SN2):
  - Reagents: Strong acids or Lewis acids (e.g., ZnCl2).
  - When to Use: When alcohols need to be converted into reactive substrates for further reactions.
- Addition Reactions of Alkenes and Alkynes:
  - Reagents: Water (H2O) with acid catalyst (like H2SO4) in acid-catalyzed hydration.
  - When to Use: To convert alkenes and alkynes to alcohols.
- Reductions of Carbonyls:
  - Reagents:
  - Catalytic Hydrogenation: Using diatomic hydrogen ( $H_2$ ) with catalysts such as Pt, Pd, or Ni.
  - Sodium Borohydride (NaBH4): Reduces aldehydes and ketones.
  - Lithium Aluminum Hydride (LiAlH4): Reduces aldehydes, ketones, carboxylic acids, and esters.
  - When to Use: When converting carbonyl compounds to alcohols.
Reactions with Alcohols:
- Nucleophilic Substitutions:
  - Reagents: Strong acids or Lewis acid catalysts (like ZnCl2), Tetrabutyl ammonium fluoride (TBAF) if necessary.
  - When to Use: When alcohols are used as nucleophiles that need further reactions.
- Conversion of Alcohols to Tosylates:
  - Reagents: Tosyl chloride (TsCl) and a base (like pyridine).
  - When to Use: To create better leaving groups before substitution.
- Conversion to Alkyl Bromides and Alkyl Chlorides:
  - Reagents:
  - Phosphorus Tribromide (PBr3) for bromides.
  - Thionyl Chloride (SOCl2) in pyridine for chlorides.
  - When to Use: When converting primary or secondary alcohols to better electrophiles.
Oxidation of Alcohols:
- Reagents:
 - Chromic Acid ( $H_2CrO_4$ ): For oxidation to carbonyls.
 - Pyridinium Chlorochromate (PCC): Offers controlled oxidation.
 - Swern Oxidation: Using $DMSO$ , $COCl2$ , and $Et3N$ .
 - When to Use: When converting alcohols to carbonyl compounds like aldehydes or ketones.