Ethers & Epoxides

Uses Galore 1

        General Anesthesia Starter Fluid Antibiotics Pheromones Marijuana Gasoline additives Antifreeze Polyesters

Ethers & Epoxides

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  R-O-R’ Epoxides—cyclic 3-membered ring ethers

Ethers & Epoxides

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 Name each alkyl or aryl group in alphabetical order, followed by ether H 3 C O CH 3 H 3 C O CH 3 O

Nomenclature of Ethers

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 More complex structures require the naming of the –OR group as an alkoxy group. Smaller alkoxy is named as substituent O CH 3 H 3 C OH O CH 3 O H 3 C O CH 3 O

Nomenclature of Ethers

H 3 C CH 3 5

        Colorless Relatively pleasant odors Lower bp than ROH with equal C’s Almost same bp as equivalent HC Cannot form H-bonds with itself Can form H-bonds with ROH Low MW soluble in H 2 O Less dense than H 2 O

Physical Properties of Ethers

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    Relatively inert Makes ethers excellent solvents Used to extract organic cpds from natural sources May oxidize over time to peroxides ◦ Test papers detect peroxides ◦ Shaken with FeSO 4 reduces peroxides CH 3 CH 2 OCH 2 CH 3 + O 2  CH 3 CH 2 OCHCH 3 OOH

Ethers as Solvents

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   Victor Grignard—1912 Nobel in Chemistry When Mg turnings (pieces) are stirred with an ether soln of either alkyl or aryl halide, exothermic rxn occurs Mg bonds to halogen as does carbon R—X + Mg dry ether  R— Mg X

The Grignard Reagent: an organometallic compound

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 Though ethers are not normally shown as part of the Grignard reagent, they do play an important role as Lewis bases and stabilize the Mg with lone pairs R—Mg—X

The Grignard Reagent: an organometallic compound

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  2 most common ethers used in Grignard preparation ◦ diethyl ether ◦ tetrahydrofuran (THF) Ether must be perfectly dry…no H 2 O or ROH ether CH 3 —I + Mg  CH 3 MgI

The Grignard Reagent: an organometallic compound

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 Alkyl or aryl group is usually negatively charged and Mg is positively charged  R—MgX Carbanion is formed ◦ Strong base ◦ ◦ Conjugate base of HC(weak acids) Grignard reagents react vigorously with weak acids like H 2 O or with any cpd with OH, SH, or NH

The Grignard Reagent: an organometallic compound

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R —MgX + H —OH  R — H stronger base stronger acid weaker acid + Mg 2+ (OH) X weaker base  This is why the ether must be perfectly dry MgBr H + H 3 C OH + H 3 C O MgBr

The Grignard Reagent: an organometallic compound

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  Rxn of Grignard with H 2 O can be useful in making a radiolabeled cpd If heavy water (deuterium oxide), D 2 O, is used, then D can be substituted for X H 3 C Br Mg ether H 3 C MgBr D 2 O H 3 C D

The Grignard Reagent: an organometallic compound

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 Prepare CH 3 CHDCH 3 from CH 2 =CHCH 3

The Grignard Reagent: an organometallic compound

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   Organometallic cpds contain a C-metal bond Acetylides (R-C=C ) act similarly to Grignard reagents Organolithium cpds are also useful in synthesis rxns R — X + 2 Li  R — Li + Li + X -

The Grignard Reagent: an organometallic compound

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 Most important ether is diethyl ether ◦ Made from ethanol and sulfuric acid at 140˚C   If at 180˚C, ethene is made Conditions are important H 3 C OH + H 3 C OH H 2 SO 4 140 °C H 3 C O CH 3 + H 2 O

Preparation of Ethers

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  The preparation of ethene occurs by E2 By what mechanism does the preparation of diethyl ether occur?

H 3 C OH + H 3 C OH H 2 SO 4 140 °C H 3 C O CH 3 + H 2 O

Preparation of Ethers

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   t-butyl methyl ether (MTBE) Octane # enhancer Use has declined due to health concerns CH 3 H + H 3 C OH + H 2 C CH 3 H 3 C O CH 3 CH 3 H 3 C

Preparation of Ethers

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 Write the mechanism of the preparation of MTBE.

Preparation of Ethers

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 Williamson Synthesis ◦ 1 st step—ROH is converted to alkoxide by treatment with reactive metal like Na or K or metal hydride ◦ 2 nd step—S N 2 displacement btw alkoxide and alkyl halide 2 RO H + 2Na  2 RO Na + + H 2 RO Na + + R’ —X  RO R’ + Na + X -

Preparation of Ethers

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 Williamson Synthesis ◦ Write an equation for the synthesis of CH 3 OCH 2 CH 2 CH 3 using Williamson method

Preparation of Ethers

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  With lone pair on O, ethers are Lewis bases React with strong acids, Lewis acids, and boron halides H R—O—R’ + H + R—O—R’ R—O—R’ + Br—B—Br Br

Cleavage of Ethers

R—O—R’ Br—B—Br Br 22

  Similar to rxn of ROH and strong acids If R and R’ are 1˚or 2˚, bond to O can be broken by strong nucleophile like I or Br via S N 2 H 3 C CH 3  CH 3 O + HI H 3 C + H O CH 3 I CH 3 O CH 3 + BBr 3 1.  2. H 2 O

Cleavage of Ethers

OH + H 3 C Br 23

 If R or R’ is 3˚, a strong nucleophile is not required since rxn will occur by S N 1 (or E1) mechanism O CH 3 CH 3 H 3 C H + H 2 O OH + H 3 C H 3 C OH CH 3

Cleavage of Ethers

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 Write the steps of the mechanism for the first rxn on slide 29: H 3 C CH 3  CH 3 O + HI H 3 C + H O CH 3 I CH 3

Cleavage of Ethers

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   Prior to 1846, asphyxiation, pressure on nerves, narcotics, ROH William T.G. Morton in 1846 removed tumor from jaw using diethyl ether as general anesthetic Ceased being used due to flammability, side effects, slow action

Ether & Anesthetics

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 Also known as oxiranes ◦ 3-membered rings containing 1 oxygen atom  H H H 3 C H 3 C O O O H CH 3 H CH 3 Most important is ethylene oxide ◦ Used as raw material for production of ethylene glycol Ag catalyst H 2 C CH 2 + O 2 250 °C, pressure O

Epoxides

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 Defoliate hardwood trees in NE  Pheromone disparlure (H 3 C) 2 HC(H 2 C) 4 (CH 2 ) 9 CH 3   H O Alternative to pesticide H

Gypsy Moth’s Epoxide

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  Much more reactive than ordinary ethers due to the strain on the 3-membered ring Products will show that ring opens H + H O + H 2 O O  ~8.2 billion lbs of (CH 2 ) 2 (OH) 2 are produced annually in this manner

Reactions of Epoxides

OH 29

 Show mechanism of previous rxn:

Reactions of Epoxides

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 Other nucelophiles add in a similar way

Reactions of Epoxides

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 Most common other than epoxides are 5 and 6-membered rings O O O tetrahydrofuran tetrahydropyran O 1,4-dioxane

Cyclic Ethers

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 THF ◦ Useful solvent ◦ ◦ Miscible in H 2 O Often superior to diethyl ether for preparation of Grignard reagents

Cyclic Ethers

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    Macrocyclic polyethers Crowns Form complexes with Na + , K + Antibiotics are often crown cpds etc [18]crown-6

Cyclic Ethers

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 Nonactin ◦ ◦ Selectively binds to K + in presence of Na + Allows for transport of K + but not Na +

Cyclic Ethers

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