Ethers and Epoxides Structure Ethers have two organic groups (alkyl, aryl, or vinyl) bonded to the same oxygen atom. R groups are identical = symmetrical ether R groups are different = unsymmetrical ether Oxygen is sp3 hybridized Nearly tetrahedral angle, depends on the R group Oxygen atom gives a slight dipole moment

Cyclic ethers contain oxygen atom(s) incorporated in a ring. Three-membered cyclic ethers are called epoxides. Epoxides Angle strain (60°) More reactive than other ethers

Nomenclature Ethers Common names – simple ethers are named by identifying the two organic substituents (alphabetically) and adding the word ether. Ethyl methyl ether Diethyl ether Cyclopentyl isopentyl ether

Nomenclature Ethers Common names – simple ethers are named by identifying the two organic substituents (alphabetically) and adding the word ether. IUPAC – use the more complex alkyl group as root name, and the rest of the ether as an alkoxy group.

Nomenclature Ethers Common names – simple ethers are named by identifying the two organic substituents (alphabetically) and adding the word ether. IUPAC – use the more complex alkyl group as root name, and the rest of the ether as an alkoxy group. 2-methoxybutane 1-ethoxy-3-methylpentane 1,4-diisopropoxybutane

Cyclic Ethers

Epoxides The oxygen is a substituent on the parent chain, its position is identified with 2 numbers followed by the word epoxy. The parent is the oxirane, groups connected to the epoxide are substituents

Physical Properties Ethers have generally low BP due to small polarities and lack of intermolecular hydrogen bonding. Somewhat similar to alkanes of comparable molecular weight.   Ethers generally dissolve well in water up to 4-5 carbons, they can participate in H-bonding forces with water Nonpolar solutes dissolve better in ether than in alcohol

Preparation of Ethers A. From Alcohols (internal dehydration) Called condensation reaction: 2 molecules are combined into a larger molecule while, at the same time, giving a smaller molecule. Best for making symmetrical ethers formed from unbranched primary alcohols. Industrial method, not good lab synthesis. If temp. is too high, alkene forms, elimination predominates with 2° and 3° alcohols. Diols can cyclize to form 5- or 6-membered rings.  The mechanism

B. From Alkyl Halides via Williamson Reaction Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH or a metal.

B. From Alkyl Halides via Williamson Reaction Alkoxides prepared by reaction of an alcohol with a strong base such as sodium hydride, NaH or a metal. Williamson reaction, the best method for the preparation of ethers, is the reaction of metal alkoxides and primary alkyl halides. 2° and 3° alkyl halides are not suitable, the alkoxide ion is strong enough base to bring about eliminations. Phenyl halides do not generally undergo substitutions.

Preparation of Epoxides A. From Alkenes via the Halohydrin route

B. From Alkenes via Peroxyacids The peroxycarboxylic acid is reduced to a carboxylic acid. The alkene is oxidized to an epoxide. 3 commonly used oxidizing agents: meta-chloroperoxybenzoic acid (MCPBA), magnesium salt of monoperoxyphthalic acid (MMPP), peroxyacetic acid

Reactions of Ethers and Epoxides A. Acid-Catalyzed Cleavage of Ethers by Concentrated HX Requires strong acid and good nucleophile; 57% conc aq HI or 48% conc aq HBr HCl less effective because weaker nucleophile in water than I– or Br– Cleavage of 1° or 2° alkyl ethers is by an SN2 pathway: Cleavage of 3° alkyl ether is by an SN1 pathway:

B. Ring Opening Reactions of Epoxides Ring strain associated with 3-membered ring causes epoxides to undergo a variety of ring-opening reactions. Nucleophilic substitution at one carbon atom with oxygen as leaving group. Regioselectivity depends on the pH conditions. Cleavage under acidic conditions, a mechanism: Cleavage under basic conditions, a mechanism:

Spectroscopy A. Mass spectrometry cleavage to form oxonium ion or loss of either alkyl group

Spectroscopy B. Infrared spectroscopy ROR stretch, 1050-1150 cm–1 ROAr stretch, 1200-1275 cm–1

Spectroscopy C. UV/visible spectroscopy need conjugated system D. 1H NMR spectroscopy CH–O–C, 3-4.5 ppm (downfield due to O prox.) CH–O–C epoxide, 2.5 (upfield due to strain) E. 13C NMR spectroscopy C attached to O are deshielded (shifted downfield), 50-80 ppm