Alcohols, Ethers, and Epoxides - Synthesis | Organic Chemistry 1

The alcohols, ethers, and epoxides are studied in this chapter: properties and naming of alcohols, synthesis of alcohols (SN reaction, reduction of carbonyls, organometallics), Williamson ether synthesis, intramolecular Williamson epoxide synthesis

Properties of Alcohols

Alcohol:

A compound having the general structure ROH. An alcohol contains a hydroxy group (OH group) bonded to an sp3 hybridized carbon atom 

 

General properties:
 

  • Alcohols exhibit molecular polarity due to the electronegativity of oxygen
  • Alcohols have an hydrophobic part (the carbon chain) and and hydrophilic part (the OH group):
    - alcohols having less than 6 carbons are soluble in water
    - alcohols having 6 or more carbons are insoluble in water because the nonpolar alkyl portion is too large to dissolve H2O
    - alcohols of any size are soluble in organic solvents

 

  • Hydroxy functional groups form hydrogen bonds with other alcohol molecules ⇒ alcohols have a higher boiling and melting points compared to the corresponding alkanes

 

  • Alcohols are amphoteric: they can be deprotonated by strong bases or protonated by strong acids

 

Nomenclature of Alcohols

How to name an alcohol:
 

The -ane ending of the corresponding alkane is replaced by -anol

  1. Find the longest carbon chain containing the carbon bonded to the OH group

  2. Number the carbon chain starting from the end closest to the OH group (if equal, start with the end closest to the first substituent)

  3. Write the number corresponding to the OH location before the parent name
    Use the suffixes diol, triol ... if there is more than one OH
    When an OH group is bonded to a ring, the ring is numbered beginning with the OH group (the "1" is usually omitted from the name)

  4. Identify the substituents and assign locants

  5. Assemble the substituents alphabetically as prefixes

 

Preparation of Alcohols by SN Reactions

 


Mechanism: SN2 reaction
 


 

As in all SN2, the reaction works best for CH3X and primary alkyl halides. However, these synthetic conditions also lead to the formation of alkenes by E reactions. To avoid competition between SN and E reactions, the halogen atom can be replaced by a better leaving group (such as acetate CH3COO-)

 

Synthesis of Alcohols by Reduction of Carbonyls

Carbonyl groups:  

Functional groups composed of a C=O bond. They are formed by oxidation of alcohols using Na2Cr2O7 or PCC

​​​​Carbon atom is less electronegative than oxygen: it is poor in electrons and will react as an electrophile. On the contrary, oxygen of a carbonyl group is nucleophilic

 

Reduction of carbonyls:



Lithium aluminium hydride (LiAlH4) and sodium borohydride (NaBH4) contain a polar metal-hydrogen bond which is a source of nucleophilic hydride H-

Mechanism:

  1. Nucleophilic attack of H- - Formation of a carbon-hydrogen bond


     
  2. Protonation of the alkoxide

 

 

​​​Oxydation and reduction of alcohols:

Primary alcohol:

Secondary alcohol:

 

Synthesis of Alcohols with Organometallics

Organometallics:

Chemical compounds containing at least one chemical bond between a carbon and a metal
​

3 common types of organometallics R-M (with R = alkyl chain):

  • alkyl lithium RLi
  • organomagnesium or Grignard reagent RMgBr
  • organocuprates or Gilman reagent R2CuLi

 

Reaction with aldehydes and ketones:



Mechanism: addition of R'- and H+ to the carbonyl
Addition to aldehydes forms a secondary alcohol while addition to ketones forms a secondary alcohol

  1. Nucleophilic attack of R'- - Formation of a carbon-carbon bond


     
  2. Protonation of the alkoxide


Other Reactions:
 

Strong reaction with water:


 

Carbon-carbon coupling reaction with Gilman reagent:

Synthesis of Ethers

Ether:

A class of organic compounds that contain an oxygen atom connected to two alkyl or aryl groups

 

Williamson ether synthesis:



Mechanism: SN2 reaction
The reaction works best for CH3X and primary alkyl halides

Synthesis of Epoxides

Epoxide:

A cyclic ether having the oxygen atom as part of a three-membered ring

 

Intramolecular Williamson epoxide synthesis:



Mechanism:

  1. Deprotonation of the hydroxy group - Formation of an alkoxide


     
  2. Intramolecular SN2 reaction