C h a p t e r T h i r t e e n: Ethers and Epoxides
O
OH OH
Benz[a]pyrene diol epoxide, a potent carcinogen which initiates mutagenesis by intercalation into double-stranded DNA
CHM 323: Summary of Important Concepts
YConcepts for Chapter 13: Ethers and Epoxides I. Nomenclature and Properties A. IUPAC 1. R–O–R' alkyl alkyl ether a. if R = R', dialkyl ether B. Some common ethers
O diethyl ether tetrahydropyran (or just ether)O (THP)
O O 1,2-dimethoxyethane 1,4-dioxane O (DME) O
O tetrahydrofuran oxirane or ethylene oxide O (THF)
C. Ethers are usually used as solvents; they are relatively inert II. Preparations of Ethers A. Acid-catalyzed condendsation 1. Condensation of two moles of a primary alcohol
H SO 2 RCH OH 2 4 RCH OCH R + H O 2 ))))) ∆ ™ 2 2 2
B. Williamson ether synthesis 1. R'X is methyl or 1 E 2. RO - M + can be from any alcohol 3. works well for cyclic ether synthesis
RO - M + + R'–X 6 R–O–R' + M + X - C. Solvomercuration-demercuration 1. is analogous to oxymercuration-demercuration synthesis of ROH 2. difference is to use an alcohol instead of water in the first step
OR OR
Hg(O 2CCH 3)2 * NaBH 4 * RCH=CH )))))) ™ RCHCH –Hg(O CCH ) )))) ™ RCHCH 2 THF, ROH 2 2 3 -OH 3
71 III. Reactions of Ethers A. Peroxidations 1. A free radical-based reaction a. forms explosive peroxyethers
RCH 2–O–R' + O 2 6 RCH–O–R' * OOH
B. Acid-catalyzed ether cleavage 1. Mechanism is sequential protonation-substitution
R–O–R' + xs H–X 6 R–X + R'–X + H 2O C. Claisen rearrangement 1. A concerted, pericyclic rearragnement of aryl allyl ethers
O O O OH
) H
IV. Preparations of epoxides (oxiranes) A. Epoxidation of alkenes
O 2 R R R O R2 H3C OOH
O 1 H R1 H R
H3C OH
B. Halohydroxylation-epoxidation of alkenes a. intramolecular anti displacement of a halide
2 R Br 2 R R 2 R R Br R NaOH 2 H 1 1 H O 1 H O H R 2 HO R 2 H O R
72 V. Reactions of epoxides (oxiranes) A. Additions of RM to oxirane (ethylene oxide) 1. A two carbon homologation reaction
O 1. ether OH RMgX + + R 2. H 3O
B. Additions of nucleophiles to epoxides under basic conditions 1. nucleophiles attack epoxide at less substituted carbon 2. SN2-like: inversion of configuration 3. example:
O OH + NH 3 H2N R R
C. Additions of nucleophiles to epoxides under acidic conditions 1. nucleophiles attack epoxide at more substituted carbon 2. SN1-like: positively charged, carbocation-like intermediates 3. example:
Br O + HBr HO R R
73 74 1. Provide the major product that is produced when the compounds below are subjected to the stated reaction conditions, including stereochemistry when appropriate. If there is no reaction, indicate so by writing "NR".
a.
CH 3ONa
O CH 3OH
b. O
1. Hg(OCCH3)2 , CH 3CH 2OH - 2. NaBH 4, OH
2. Prepare the following compounds from the starting materials given and any other reagents that you require. a. O from
O b. O from
Br
75 O c. O from
3. Provide a clear, reasonable reaction mechanism that explains the following observed chemical transformation:
xs HBr Br Br O
76 4. The most stable conformation of 1,3-dioxan-5-ol is the chair from that has the OH group in an axial orientation. Suggest a reasonable explanation for this fact.
OH
OO
1,3-dioxan-5-ol
77 5. When (Z)-2-butene is reacted with t-C H OOH in t-C H OH using a catalytic amount of A A 4 9 4 9 OsO 4 , product results. When is treated with two equivalents of sodium amide, followed by one equivalent of 1,2-dibromoethane, product B, which was determined to contain no halogens, was isolated. When B is treated with four equivalents of anhydrous hydrogen bromide, an equimolar mixture of 1,2-dibromoethane and product C is produced. Product C was found to undergo a rapid reaction with two equivalents of the strong base sodium amide, to provide D, a gas which contained no halogens and having a strong, onion-like odor. Provide structural formulas for A - D.
cat OsO 4 t-C H OOH 1. 2 NaNH C6H12 O2 (Z)-2-butene 4 9 A 2 t -C 4H9OH 2. 1,2-dibromoethane B
4 equiv HBr
1,2-dibromoethane + C H 2 NaNH 4 6 2 C D
78 6. When one mole of (2 R,6 S)-6-bromo-2-heptanol is reacted with one mole of the strong base - + [(CH 3)2CH] 2N Li in DMSO, a cyclic ether product forms. a. Provide a reasonable, clear, detailed reaction mechanism to illustrate this reaction.
b. Does the product rotate plane polarized light? Clearly explain the reasoning that led to your answer.
79 7. Provide a chemically reasonable, clear, detailed reaction mechanism that explains how diallyl ether, CH 2=CHCH 2OCH 2CH=CH 2, is formed when allyl alcohol, CH 2=CHCH 2OH, is heated with H 2SO 4.
8. Here’s a reprise of problem 10 from Chapters 6 & 7: like HCl, alkanols can add to double bonds in the presence of acid catalysts. For instance:
H SO OH + 2 4 CH Cl O 2 2 O O
a. Acoount for the formation of the product of this reaction using an accurate, clear, detailed reaction mechanism.
b. Would this be considered to be a Markovnikov or an antiMarkovnikov addition? Briefly explain the reasoning that led you to your answer.
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