Ethers

• Ethers have the largest bond angles: 112 degrees
• Ether acts as a hydrogen bond acceptor
• Alcohol acts as a hydrogen bond donor
• The boiling point of ether is lower than alcohol
• Ethers are unreactive and thus used as solvents for organic reactions

  ○ Dissolve a wide variety of organic compounds

  ○ Low boiling point
• Crown Ethers


  Ethers that interact with metals (Full or partial positive charge)
• Grignard Reagents


  ○ Formed in the presence of an ether (such as diethyl ether)

  ○ Lone pairs on the oxygen atom stabilize the charge on the magnesium atoms (interactions is weak)

  
• Nomenclature of Crown Ethers

  X-crown-Y

  • X indicates the total number of atom in the ring and Y represents the number of oxygen atoms
• 12-crown-4


  Solvates Li+

  
• 15-crown-5


  Solvates Na+

  
• 18-crown-6


  Solvates K+

  
• Crown Ethers

  A) 12-crown-4

  B) 15-crown-5

  C) 18-crown-6

  
• Williamson Ether Synthesis

  A) NaH

  B) RX

  
• Alkoxymercuration-demercuration of ethers

  markovnikov reaction, anti-addition

  A) Hg(OAc)2

  B) ROH

  C) NaBH4

  D) RO

  E) H

  
• Acidic cleavage

  heated with a concentrated solution of a strong acid (HX)

  A) HX

  
• Acidic cleavage example:

  A) OH

  B) RX

  
• Autooxidation

  Ethers undergo autoxidation in the presence of atmospheric oxygen to form hydroperoxides

  A) O2

  B) OOH

  
• Oxirane or Epoxide


  Cyclic ethers containing a three-membered ring system.● This ring system is more reactive than other ethers because it has significant ring strain.

  A) Oxirane

  B) Oxetane

  C) Oxolane

  D) Oxane

  
• Preparation of Epoxide with Peroxy acids

  commonly used peroxy acid: MCPBA, RCO3H

  A) RCO3H

  
• Preparation of Epoxides from Halohydrins

  Halohydrins can be converted into epoxides upon treatment with a strong base

  Reaction below summarizes alkanes -> halohydrins -> epoxides

  A) Br2

  B) NaOH

  
• Summary of epoxidation

  Substituents that are cis to each other remain cis. Same goes for trans

  A) MCPBA

  B) Br2

  C) NaOH

  
• When forming an epoxide that is chiral, each of the previous methods will provide a racemic mixture.
• Enantioselective Epoxidation


  • To favor formation of just one enantiomer, we must favor epoxidation at one face of the alkene through a chiral catalyst called Sharpless' catalyst

  
• Sharpless epoxidation

  A) (-)-DET

  B) (+)-DET

  
• Ring-Opening Epoxide

  A) strong nucleophile

  B) NaOH

  C) H3O

  D) acid

  
• Ring Opening conditions

  The opening of Epoxide exhibit important features

  1. Regiochemistry

  • Favors attack at the less substituted position
  • When the epoxide possesses only primary and secondary positions, this effect will be dominant

  2. Electronic effect

  • Favors attack at the more substituted position
  • When the epoxide possesses a tertiary position, this effect will be dominant.

  3. Stereochemistry - When the attack takes place at a chiral center, inversion of configuration is observed
• Thiol


  Sulfur analogs of alcohols contain an SH group in place of an OH group

  
• Thiol nomenclature

  When another functional group is present in the compound, the SH group is named as a substituent and is called a mercapto group
• Oxidation of Thiol

  Thiols easily undergo oxidation to produce disulfides. This requires an oxidizing reagent

  A) Br2

  B) NaOH / H2O

  
• Formation of Thiol

  A) NaSH

  
• Sulfides


  The sulfur analogs of ethers, also called thioethers.

  
• Sulfide nomenclature

  When another functional group is present in the compound, the S-R group is named as a substituent and is called alkylthio group
• Formation of Sulfide from Thiol

  also follows Williamson ether synthesis

  A) NaOH

  B) RX

  
• Oxidation of Sulfide

  strong reagent to reach 3rd oxidation: 2 H2O2

  weak reagent to reach 2nd oxidation: NaIO4

  A) Sulfide

  B) Sulfoxide

  C) Sulfone

  
• Acid-catalyzed Epoxides

  Ring-opening reactions can also occur under acidic conditions

  A) HX

  
• Thiol reactions summary

  A) NaSH

  B) NaOH/H2O

  C) Br2

  D) HCl

  
• Sulfide reactions

  A) NaOH

  B) RX

  C) MeX

  D) H2O2

  E) NaIo4

  F) H2O2

  G) sulfide

  H) Sulfoxide

  I) sulfone

  
• Ring-opening epoxide

  1, Strong nucleophiles:

  • NaOR
  • NaCN
  • NaSR
  • RMgBr
  • LiAlH4

  2, acidic workup: H3O+