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• An ether group includes an oxygen atom that is bonded to TWO –R groups:
• –R groups can be alkyl, aryl, or vinyl groups.
• Would the compound below be considered an ether?
14.1 Introduction to Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -1
O
O
• Compounds containing ether groups are quite common.
14.1 Introduction to Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -2
• Common names are used frequently:1. Name each –R group.
2. Arrange them alphabetically.
3. End with the word “ether.”
14.2 Naming Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -3
• IUPAC systematic names are often used as well:1. Make the larger of the –R groups the parent chain.
2. Name the smaller of the –R groups as an alkoxy substituent.
• Practice with SKILLBUILDER 14.1.
14.2 Naming Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -4
• Name the following molecule.
• Draw the structure for (R)‐1‐methoxycyclohexen‐3‐ol.
14.2 Naming Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -5
O Cl
• The bond angle in ethers is very similar to that found in water and in alcohols.
• Is the oxygen atom in an ether sp3, sp2, or sp hybridized?
• How do the –R groups affect the bond angle?
14.3 Structure and Properties of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -6
• In Chapter 13, we learned that due to hydrogen‐bonding (H‐bonding), alcohols have relatively high boiling points.
• What is the maximum number of H‐bonds an alcohol can have?
• Draw an H‐bond between an ether and an alcohol.
• What is the maximum number of H‐bonds an ether can have?
14.3 Structure and Properties of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -7
• In Chapter 13, we learned that due to hydrogen‐bonding (H‐bonding), alcohols have relatively high boiling points.
• Would you expect the boiling point of an ether to be elevated similar to alcohols?
• WHY or WHY not?
14.3 Structure and Properties of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -8
• Explain the boiling point trends below using all relevant intermolecular attractions.– Trend 1:
– Trend 2:
14.3 Structure and Properties of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -9
• Ethers are often used by organic chemists as solvents:– Relatively low boiling points allow them to be evaporated
after the reaction is complete.
– Their dipole moment allows them to stabilize charged or partially charged transition states. HOW?
– They are NOT protic. WHY is that an advantage for a solvent in many reactions?
14.3 Structure and Properties of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -10
• Metal atoms with a full or partial positive charge can be stabilized by ether solvents.
• Ethers are generally used as the solvent in Grignard reactions.
• Give another reason why an ether makes a good solvent in this reaction.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -11
• Crown ethers have been shown to form especially strong attractions to metal atoms. WHY?
• Note how many carbon atoms separate the oxygen.
• Why are they called CROWN ethers?
• Explain the numbers found in their names.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -12
• The size of the metal must match the size of the crown to form a strong attraction.
• 18‐crown‐6 fits a K+ ion just right.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -13
• Normally metal ions are not soluble in low polarity solvents. WHY?
• The crown ether–metal complex should dissolve nicely in low polarity solvents. WHY?
• Imagine how a crown ether could be used to aid reactions between ions (especially anions) and low polarity organic substrates.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -14
• The F– ion below is ready to react because the K+ ion is sequestered by the crown ether.
• Without the crown ether, the solubility of KF in benzene is miniscule.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -15
• Generally, the F– ion is not used as a nucleophile because it is strongly solvated by polar solvents.
• Such solvation greatly reduces its nucleophilic strength.
• In the presence of the crown ether and in a nonpolar solvent, the F– ion is soluble enough that it can readily attack an electrophile.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -16
• Smaller crown ethers bind smaller cations.
• Practice with CONCEPTUAL CHECKPOINT 14.4.
14.4 Crown Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -17
• Diethyl ether is prepared industrially by the acid‐catalyzed dehydration of ethanol.
• How is it a dehydration?
• Can this method be used to make asymmetrical ethers?
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -18
• The Williamson ether synthesis is a viable approach for many asymmetrical ethers.
• What happens to the halide?
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -19
• The Williamson ether synthesis is a viable approach for many asymmetrical ethers.
• The alkoxide that forms in step 1 is also a strong base.
• Are elimination products likely for methyl, primary, secondary, or tertiary alkyl halides?
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -20
• Use the Williamson ether approach to prepare MTBE.
• Consider a retrosynthetic disconnect on the t‐butyl side.
• It is better to make your retrosynthetic disconnect on the methyl side. WHY?
• Practice with SKILLBUILDER 14.2.
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -21
• Use the Williamson ether approach to synthesize the following molecule.
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -22
• Recall from Section 9.5 that oxymercuration‐demercuration can be used to synthesize alcohols.
• Is the addition Markovnikov or anti‐Markovnikov?
• Is the addition syn or anti?
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -23
• Similarly, alkoxymercuration‐demercuration can be used to synthesize ethers.
• Is the addition Markovnikov or anti‐Markovnikov?
• Is the addition syn or anti?
• Practice CONCEPTUAL CHECKPOINTs 14.8‐14.10.
14.5 Preparation of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -24
• As we mentioned earlier because they are aprotic, ethers are generally unreactive.
• However, ethers can react under the right conditions.
• Consider the ether below.
• Where are the most reactive sites?
• Is it most likely to react as an acid, base, nucleophile, electrophile, etc.?
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -25
• Ethers can undergo acid‐promoted cleavage.
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -26
• Draw a complete mechanism and predict the products for the following acid‐promoted cleavage.
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -27
• To promote cleavage, HI and HBr are generally effective.
• HCl is less effective, and HF does not cause significant cleavage.
• Explain the trend above considering the relative strength of the halide nucleophiles.
• Why is the cleavage considered acid‐promoted rather than acid‐catalyzed?
• Practice with CONCEPTUAL CHECKPOINT 14.11.
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -28
• Predict products for the reaction below, and draw a complete mechanism.
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -29
• Recall from Section 11.9 that ethers can undergo autooxidation.
• Hydroperoxides can be explosive, so laboratory samples of ether must be frequently tested for the presence of hydroperoxides before they are used.
• The autooxidation occurs through a free radical mechanism.
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -30
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -31
• Recall that the net reaction is the sum of the propagation steps:
14.6 Reactions of Ethers
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -32
• For cyclic ethers, the size of the ring determines the parent name of the molecule.
• Oxiranes are also known as epoxides.
• Which cyclic ether system do you think is most reactive? WHY?
14.7 Naming Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -33
• An epoxide can have up to 4 –R groups.
• Although they are unstable, epoxides are found commonly in nature.
14.7 Naming Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -34
• There are two methods for naming epoxides:1. The oxygen is treated as a side group, and two numbers are
given as its locants.
2. Oxirane is used as the parent name.
14.7 Naming Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -35
• Name the molecules below by both methods if possible.
• Practice CONCEPTUAL CHECKPOINTs 14.12 and 14.13.
14.7 Naming Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -36
• Recall from Section 9.9 that epoxides can be formed when an alkene is treated with a peroxy acid.
• MCPBA and peroxyacetic acid are most commonly used.
14.8 Preparation of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -37
• Recall that the process is stereospecific.
14.8 Preparation of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -38
• Epoxides can also be formed from halohydrins.
• What is a halohydrin?
• How are halohydrins formed from alkenes?
• When a halohydrin is treated with NaOH, a ring‐closing reaction can occur.
14.8 Preparation of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -39
14.8 Preparation of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -40
• Assess the overall stereochemistry of the epoxidation that occurs through the halohydrin intermediate.
• Practice with SKILLBUILDER 14.3.
14.8 Preparation of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -41
• The epoxidation methods we have discussed so far are NOT enantioselective.
• Draw the products.
14.9 Enantioselective Epoxidation
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -42
• The epoxidation forms a racemic mixture because the flat alkene can react on either face.
14.9 Enantioselective Epoxidation
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -43
• To be enantioselective at least one of the reagents (or the catalyst) in a reaction must be chiral.
• The Sharpless catalyst forms such a chiral complex with an allylic alcohol.
14.9 Enantioselective Epoxidation
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -44
• The desired epoxide can be formed if the right catalyst is chosen. Note the position of the –OH group.
• How does the catalyst favor just one epoxide product?
• Practice with CONCEPTUAL CHECKPOINT 14.16.
14.9 Enantioselective Epoxidation
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -45
• Because of their significant ring strain, epoxides have great synthetic utility as intermediates.
• Propose some reagents that might react with an epoxide to provide a specific functional group.
• Propose some reagents that might react with an epoxide to alter the carbon skeleton.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -46
• Strong nucleophiles react readily with epoxides.
• Predict whether each step is product‐ or reactant‐favored, and explain WHY.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -47
• In general, alkoxides are not good leaving groups.
• The ring strain associated with the epoxide increases its potential energy making it more reactive.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -48
• The epoxide reaction is both more kinetically and more thermodynamically favored. WHY?
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -49
• Epoxides can be opened by many other strong nucleophiles as well.
• Both regioselectivity and stereoselectivity must be considered.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -50
• Given that the epoxide ring‐opening is SN2, predict the outcome of the following reactions.
• Pay attention to regio‐ and stereoselectivity. Explain WHY.
• Practice with SKILLBUILDER 14.4.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -51
O
• Acidic conditions can also be used to open epoxides.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -52
• Water or an alcohol can also be used as the nucleophile under acidic conditions.
• Predict the products and draw a complete mechanism.
• Antifreeze (ethylene glycol) is made industrially by this method.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -53
• Propose an explanation for the following regiochemical observations.
• Consider both steric and electronic effects (induction).
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -54
• If the nucleophile preferentially attacks the tertiary carbon under acidic conditions, is the mechanism likely SN1 or SN2?
• Considering the observations below, is the mechanism likely SN1 or SN2?
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -55
• When the nucleophile attacks a tertiary center of the epoxide, the intermediate it attacks takes on some carbocation character (SN1), but not completely.
• Give reaction conditions for the following reaction.
• Practice with SKILLBUILDER 14.5.
14.10 Ring‐opening of Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -56
• Sulfur appears just under oxygen on the periodic table.
• Sulfur appears in THIOLS as an –SH group analogous to the –OH group in alcohols.
• The name of a compound with an –SH group ends in “thiol” rather than “ol.”
• Note that the “e” of butane is not dropped in the name of the thiol.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -57
• Thiols are also known as mercaptans.
• The –SH group can also be named as part of a side group rather than as part of the parent chain.
• The mercaptan name comes from their ability to complex mercury.
• 2,3‐dimercapto‐1‐propanol is used to treat mercury poisoning. WHY? Draw its structure.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -58
• Thiols are known for their unpleasant odor.
• Skunks use thiols as a defense mechanism.
• Methanethiol is added to natural gas (methane) so that gas leaks can be detected.
• Your nose is a very sensitive instrument.
• The hydrosulfide ion (HS–) is a strong nucleophile and a weak base.
• HS– promotes SN2 rather than E2.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -59
• Predict the outcome of the following reactions, and draw a complete mechanism.
• Practice with CONCEPTUAL CHECKPOINT 14.22.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -60
• Thiols have a pKa of about 10.5.
• Recall that water has a pKa of 15.7.
• Predict whether the equilibrium below will favor products or reactants and draw the mechanism.
• Thiolates are excellent nucleophiles.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -61
thiolate ion
• Once a thiolate forms, it can attack Br2 to produce a disulfide.
• How does the oxidation number change?
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -62
• Disulfides can be reduced by the reverse reaction.
• The interconversion between thiol and disulfide can also occur directly via a free radical mechanism. Propose a mechanism.
• The bond dissociation energy of a S–S bond is only about 53 kcal/mol. WHY is that significant?
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -63
• Sulfur analogs of ethers are called SULFIDES or THIOETHERS.
• Sulfides can also be named as a side group.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -64
• Sulfides are generally prepared by nucleophilic attack of a thiolate on an alkyl halide.
• How are thiolates generally prepared?
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -65
• Sulfides undergo a number of reactions:1. Attack on an alkyl halide:
– The process produces a strong alkylating reagent that can add an alkyl group to a variety of nucleophiles.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -66
• Sulfides undergo a number of reactions:2. Sulfides can also be oxidized.
– Sodium meta‐periodate can be used to form the sulfoxide.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -67
• Sulfides undergo a number of reactions:2. Sulfides can also be oxidized.
– Hydrogen peroxide can be used to give the sulfone.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -68
• Sulfoxides and sulfones have very little double bond character.
• Which resonance contributor for each is the major contributor, and WHY?
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -69
• Because sulfides are readily oxidized, they make good reducing agents.
• Recall the ozonolysis reaction from Section 9.11.
• Practice with CONCEPTUAL CHECKPOINT 14.23.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -70
• Predict any products or necessary reagents in the reaction sequence below.
• Verify the formal charge on the sulfur in the final product above.
14.11 Thiols and Sulfides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -71
BrHS
1) NaOH
2)
• Epoxides can be used to install functional groups on adjacent carbons.
• Give necessary reagents for the reaction below.
• Practice with SKILLBUILDER 14.6.
14.12 Synthetic Strategies Involving Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -72
• By reacting an epoxide with a Grignard reagent, the carbon skeleton can be modified.
• You may think of an alkyl halide as the starting material.
14.12 Synthetic Strategies Involving Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -73
• Recall that a carbonyl can be used to install a one carbon chain between an R group and an OH group.
• An epoxide can be used to install a two carbon chain between an R group and an OH group.
14.12 Synthetic Strategies Involving Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -74
• Give necessary reagents for the reaction below.
• Practice with SKILLBUILDER 14.7.
14.12 Synthetic Strategies Involving Epoxides
Copyright 2012 John Wiley & Sons, Inc. Klein, Organic Chemistry 1e14 -75