Reactions Involving Alcohols

What are seven important reactions involving alcohols?

1. Nucleophilic substitution to form alkyl halides
   • Via alteration of the hydroxyl group to make it a better leaving group
     • Protonating to form H$_{2}$O (a much better leaving group than a hydroxyl group)
     • Converting it to an ether ($ROR'$)
   • $S_{N}1$ reactions in the formation in alkyl halides
     • 2$^{o}$/3$^{o}$ alcohols and benzylic alcohols can form carbocations resulting in $S_{N}1$ reactions with the carbocation serving as a substrate:
       

       Figure 45.6: 2$^{o}$/3$^{o}$ alcohols in $S_{N}1$ reactions.

       

   • $S_{N}2$ reactions in the formation in alkyl halides
     • 1$^{o}$ alcohols and methanol
       

       Figure 45.7: 1$^{o}$ alcohols and the formation in alkyl halides: an $S_{N}2$ reaction using ethanol to create 1-bromo-ethane and water.

       

2. A lone pair of electrons from the hydroxyl's oxygen acts as a nucleophile
   • Reactions with PBr$_{3}$ and SOCl$_{2}$
     • A 1$^{o}$ or 2$^{o}$ alcohol will react with PBr$_{3}$ to form an alkyl bromide
       

       Figure 45.8: 1$^{o}$ or 2$^{o}$ alcohol reactions with PBr$_{3}$. Note, in this reaction, three alcohols are needed for the reaction to proceed in the forward direction, which creates three primary alkyl halides for every one phosphoric acid.

       

     • A 1$^{o}$ or 2$^{o}$ alcohol will react with SOCl$_{2}$ to form an alkyl chloride
       

       Figure 45.9: 1$^{o}$ or 2$^{o}$ alcohol reactions with SOCl$_{2}$. In this example, ethanol reacts with SOCl$_{2}$ to form 1-chloro-ethane.

       

   • Mesylates and tosylates preparation
     • Mesylates and tosyltates are very useful as substrates in $S_{N}2$ reactions because sulfonate ions are excellent leaving groups:
       

       Figure 45.10: Alcohols and mesylate/tosylate preparation.

       

   • Fischer Esterification, i.e. the synthesis of esters through the reaction of a carboxylic acid with an alcohol:
     $H_{3}C-COOH + HOCH_{2}CH_{3} + H_{2}SO_{4}\rightarrow H_{3}C-COO-CH_{2}CH_{3} + H_{2}SO_{4} + H_{2}O$
     

     Figure 45.11: Fischer Esterification: synthesis of esters through the reaction of a carboxylic acid with an alcohol.

     

   • Reaction with inorganic acids to form esters of inorganic acids, e.g. ATP
   • Other $S_{N}2$ reactions that attack $sp^{3}$ carbons
3. Elimination reactions
   • Alcohol dehydration to produce alkenes ($E1$ elimination):
     

     Figure 45.12: Alcohol dehydration. This process occurs most easily for tertiary alcohols, followed by secondary alcohols and then primary alcohols.

     

4. Oxidation reactions
   • Oxidation occurs in the presence of a strong oxidation agent - usually a molecule with a oxidizing metal, e.g. KMnO$_{4}$, Na$_{2}$Cr$_{2}$O$_{7}$ or PCC (C$_{5}$H$_{6}$NCrO$_{3}$Cl)
   • Alcohols oxidize to alkanes or aldehydes depending on the R group. If the R group is a hydrogen, oxidation will produce an aldehyde; if the R group is an alkyl, oxidation will produce a ketone:
     

     Figure 45.13: Oxidation of alcohols.

     

5. Reduction reactions
   • Reduction occurs in the presence of a strong reducing agent, e.g. LiAlH$_{4}$ and NaBH$_{4}$
   • In this example, a carboxylic acid is converted to an alcohol:
     

     Figure 45.14: Reduction of alcohols.

     

   • Generally speaking, the trend among organic molecules in regards to oxidation and reduction can be predicted as seen below:
     

     Figure 45.15: Reduction of organic molecules.

     

6. The pinacol rearrangement^46.2
   • The hydroxyl group can also act as a weak acid
   • The acid-catalyzed elimination of water from a 1,2-diol to yield a ketone:
     

     Figure 45.16: Pinacol rearrangement: acid-catalyzed elimination of water from a 1,2-diol to yield a ketone.