Solution: Give IUPAC names for the following compounds.

Problem 29SP Show how you would make the following ethers, using only simple alcohols and any needed reagents as your starting materials. (a) 1-methoxybutane (b) 2-ethoxy-2-methylpropane (c) benzyl cyclopentyl ether (d) trans-2-methoxycyclohexanol (e) the TIPS ether of (d) (f) cyclohexyl cyclopentyl ether

Show how you would use the Williamson ether synthesis to prepare the following ethers. You may use any alcohols or phenols as your organic starting materials. (a) cyclohexyl propyl ether (b) isopropyl methyl ether (c) 1-methoxy-4-nitrobenzene (d) ethyl -propyl ether (two ways) (e) benzyl tert-butyl ether (benzyl \(=\mathrm{Ph}-\mathrm{CH}_{2}-\)) ________________ Equation Transcription: Text Transcription: =Ph-CH2-

Problem 50SP Glycerol (propane-1,2,3-triol) is a viscous syrup with molecular weight 92 g/mol, boiling point 290 °C, and density 1.24 g/mL. Transforming the three hydroxyl groups into their trimethylsilyl ethers (using chlorotrimethylsilane and a tertiary amine) produces a liquid that flows easily, has molecular weight 309 g/mol, boiling point approximately 180 °C, and density 0.88 g/mL. Draw the structures of these two compounds and explain why glycerol has a lower molecular weight but a much higher boiling point and density.

Problem 26P Predict the major product when each reagent reacts with ethylene oxide. (a) NaOCH2CH3 (sodium ethoxide) (b) NaNH2 (sodium amide) (c) NaSPh (sodium thiophenoxide) (d) PhNH2 (aniline) (e) KCN (potassium cyanide) (f) NaN3 (sodium azide)

Problem 28P Give the expected products of the following reactions. Include a protonation step where necessary. (a) 2,2-dimethyloxirane + isopropylmagnesium bromide (b) propylene oxide + n-butyllithium (c) cyclopentyloxirane + ethyllithium

Problem 30SP Write structural formulas for the following compounds. (a) ethyl isopropyl ether (b) di-n-butyl ether (c) 2-ethoxyoctane (d) divinyl ether (e) allyl methyl ether (f) cyclohexene oxide (g) cis-2,3-epoxyhexane (h) (2R,3S)-2-methoxypentan-3-ol (i) trans-2,3-dimethyloxirane

Give a common name (when possible) and a systematic name for each compound. (a) \(\mathrm{CH}_{3} \mathrm{OCH}=\mathrm{CH}_{2}\) (b) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OCH}\left(\mathrm{CH}_{3}\right)_{2}\) (c) \(\mathrm{ClCH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) ________________ Equation Transcription: Text Transcription: CH_{3}OCH=CH_{2} CH_{3}CH_{2}OCH(CH_{3})2 ClCH_{2}CH_{2}OCH_{3} OCH_{2}CH_{3} OCH_{3} OCH_{3} OH OCH_{3} OCH_{3} CH_{3}C equiv CCH_{2}OCH_{3} OCH_{3}

Show how you would convert 3-bromocyclohexanol to the following diol. You may use any additional reagents you need. ________________ Equation Transcription: Text Transcription: HO Br HO CH_3 OH CH_{2}CH_3

Propose a fragmentation to account for each numbered peak in the mass spectrum of n-butyl isopropyl ether. Equation Transcription: Text Transcription: M^+ m/z

Problem 25P Propose a complete mechanism for the reaction of cyclopentene oxide with sodium methoxide in methanol.

Name the following heterocyclic ethers. Equation Transcription: Text Transcription: Cl CH(CH_{3})_2 CH_{3}CH_2 CH_{2}CH_3 Br OCH_{2}CH_3 Br CH_{3} CH_3

Problem 5P 1,4-Dioxane is made commercially by the acid-catalyzed condensation of an alcohol. (a) Show what alcohol will undergo condensation, with loss of water, to give 1,4-dioxane. (b) Propose a mechanism for this reaction.

Problem 8P Propose a Williamson synthesis of 3-butoxy-1,1-dimethylcyclohexane from 3,3-dimethylcyclohexanol and butan-1-ol.

Boron tribromide \(\mathrm {(BBr^3)}\) cleaves ethers to give alkyl halides and alcohols. \(\mathrm{R}-\mathrm{O}-\mathrm{R}^{\prime}+\mathrm{BBr}_{3} & \longrightarrow \mathrm{R}-\mathrm{O}-\mathrm{BBr}_{2}+\mathrm{R}^{\prime} \mathrm{Br}\) \(\mathrm{R}-\mathrm{O}-\mathrm{BBr}_{2} &+3 \mathrm{H}_{2} \mathrm{O} \longrightarrow \mathrm{ROH}+\mathrm{B}(\mathrm{OH})_{3}+2 \mathrm{HBr}\) Equation Transcription: Text Transcription: (BBr^{3}) R-O-R'+BBr_{3}{rightarrow}R-O-BBr_{2}+R'Br R-O-BBr_{2}+3 H_{2}O{rightarrow}ROH+B(OH)_{3}+2 HBr

Problem 17P Show how you would synthesize butyl isopropyl sulfide using butan-1-ol, propan-2-ol, and any solvents and reagents you need.

Mustard gas \(\mathrm{Cl}-\mathrm{CH}_{2} \mathrm{CH}_{2}-\mathrm{S}-\mathrm{CH}_{2} \mathrm{CH}_{2}-\mathrm{Cl}\), was used as a poisonous chemical agent in World War I. Mustard gas is much more toxic than a typical primary alkyl chloride. Its toxicity stems from its ability to alkylate amino groups on important metabolic enzymes, rendering the enzymes inactive. (a) Propose a mechanism to explain why mustard gas is an exceptionally potent alkylating agent. (b) Bleach (sodium hypochlorite, \(\mathrm {NaOCl}\), a strong oxidizing agent) neutralizes and inactivates mustard gas. Bleach is also effective on organic stains because it oxidizes colored compounds to colorless compounds. Propose products that might be formed by the reaction of mustard gas with bleach. Equation Transcription: Text Transcription: Cl-CH_{2}CH_{2}-S-CH_{2}CH_{2}-Cl NaOCl

Problem 38SP Show how you would convert hex-1-ene to each of the following compounds. You may use any additional reagents and solvents you need. (a) 2-methoxyhexane (b) 1-methoxyhexane (c) 1-methoxyhexan-2-ol (d) 2-methoxyhexan-1-ol (e) 1-phenylhexan-2-ol (f) 2-methoxy-1-phenylhexane

Give the structures of intermediates A through H in the following synthesis of trans-1-cyclohexyl-2-methoxycyclohexane. Equation Transcription: Text Transcription: OH H_2{S}O_4 MCPBA Hg(OAc)_{2}, CH_{3}OH NaBH_{4} HBr Mg H_{3}O^+ Na

(Another true story.) An organic lab student carried out the reaction of methylmagnesium iodide with acetone \(\left(\mathrm{CH}_{3} \mathrm{COCH}_{3}\right)\), followed by hydrolysis. During the distillation to isolate the product, she forgot to mark the vials she used to collect the fractions. She turned in a product of formula \(\mathrm{C}_{4} \mathrm{H}_{10} \mathrm{O}\) that boiled at \(35^{\circ} \mathrm{C}\). The IR spectrum showed only a weak \(\mathrm{O}-\mathrm{H}\) stretch around \(3300 \mathrm{~cm}^{-1}\), and the mass spectrum showed a base peak at \(m/z\ 59\). The NMR spectrum showed a quartet \((J=7 \mathrm{~Hz})\) of area 2 at \(\delta\ 3.5\) and a triplet \((J=7 \mathrm{~Hz})\) of area 3 at \(\delta\ 1.3\). Propose a structure for this product, explain how it corresponds to the observed spectra, and suggest how the student isolated this compound. Equation Transcription: Text Transcription: (CH_{3}COCH_{3}) C_{5}H_{10}O 35^o O-H 3300 cm^{-1} m/z 59 (J=7 Hz) delta 3.5 (J=7 Hz) delta 1.3

Problem 13P Which of the following ethers can be formed in good yield by condensation of the corresponding alcohols? For those that cannot be formed by condensation, suggest an alternative method that will work. (a) dibutyl ether (b) ethyl n-propyl ether (c) di-sec-butyl ether

Propose a mechanism for the following reaction. Equation Transcription: Text Transcription: HBr Br Br

Predict the products of the following reactions. An excess of acid is available in each case. (a) ethoxycyclohexane + HBr (b) tetrahydropyran + HI (c) anisole (methoxybenzene) + HBr Equation Transcription: Text Transcription: HBr HI HBr HI PhOCH_{2}CH_{2}-CH-CH_{2}OCH_{2}CH_{3}+HBr CH_{3}

Problem 35SP (a) Show how you would synthesize the pure (R) enantiomer of 2-butyl methyl sulfide starting with pure (R)-butan-2-ol and any reagents you need. (b) Show how you would synthesize the pure (S) enantiomer of the product, still starting with (R)-butan-2-ol and any reagents you need.

Problem 36SP (a) Predict the values of m/z and the structures of the most abundant fragments you would observe in the mass spectrum of di-n-propyl ether. (b) Give logical fragmentations to account for the following ions observed in the mass spectrum of 2-methoxypentane: 102, 87, 71, 59, 31.

The following reaction resembles the acid-catalyzed cyclization of squalene oxide. Propose a mechanism for this reaction. Equation Transcription: Text Transcription: H^+ H^{2}O CH^{2}OH OH CH_{3}

Predict the major products of the following reactions, including stereochemistry where appropriate. (a) 2,2-dimethyloxirane + \(\mathrm{H}^{+} / \mathrm{H}_{2}^{18} \mathrm{O}\) (oxygen-labeled water) (b) 2,2-dimethyloxirane + \(\mathrm{H}^{18} \mathrm{O}^{-} / \mathrm{H}_{2}^{18} \mathrm{O}\) (c) (2S,3R)-2-ethyl-2,3-dimethyloxirane + \(\mathrm{CH}_{3} \mathrm{O}^{-} / \mathrm{CH}_{3} \mathrm{OH}\) (d) (2S,3R)-2-ethyl-2,3-dimethyloxirane + \(\mathrm{H}^{+} / \mathrm{CH}_{3} \mathrm{OH}\) Equation Transcription: Text Transcription: H^{+}/H_{2}^{18}O H^{18}O^-/H_{2}^{1}8O CH_{3}O-/CH_{3}OH H^{+}/CH_{3}OH

A compound of molecular formula \(\mathrm{C}_{8} \mathrm{H}_{8} \mathrm{O}\) gives the IR and NMR spectra shown here. Propose a structure, and show how it is consistent with the observed absorptions. Equation Transcription: Text Transcription: C_{8}H_{8}O ({mu}m) (cm^{-1}) CDCl_{3} 3.9{delta} 3.8{delta} 3.2{delta} 3.1{delta} 3.0{delta} 2.9{delta} 2.7{delta} {delta}(ppm)

A new graduate student was studying the insecticidal properties of a series of polycyclic epoxides. He epoxidized alkene A using two different methods. First he used MCPBA, which gave an excellent yield of an epoxide that he labeled B. Then he treated alkene A with bromine water to form the bromohydrin, followed by 2,6-dimethylpyridine (see page 647) to form an epoxide in fair yield. To his surprise, the second method produced an epoxide (C) with different physical and chemical properties from the first. In particular, C reacts with strong nucleophiles much faster than B. Propose structures for B and C, and propose mechanisms to show why different products are formed. Explain why C reacts so much faster with strong nucleophiles. Equation Transcription: Text Transcription: H_{3}C CH_{3} MCPBA Br_{2}, H_{2}O

Tetramethyloxirane is too hindered to undergo nucleophilic substitution by the hindered alkoxide, potassium tert-butoxide. Instead, the product is the allylic alcohol shown. Propose a mechanism to explain this reaction. What type of mechanism does it follow? Equation Transcription: Text Transcription: H_{3}C CH_{3} H_{3}C CH_{3} (CH_{3})_{3}C-O- K^+ (CH_{3})_{3}C-OH H_{3}C OH CH_{3} CH_{2} CH_{3} CH_{3}

Problem 10P Show how the following ethers might be synthesized using (1) alkoxymercuration–demercuration and (2) the Williamson synthesis. (When one of these methods cannot be used for the given ether, point out why it will not work.) (a) 2-methoxybutane (b) ethyl cyclohexyl ether (c) 1-methoxy-2-methylcyclopentane (d) 1-methoxy-1-methylcyclopentane (e) 1-isopropoxy-1-methylcyclopentane (f) tert-butyl phenyl ether

Problem 11P Explain why bimolecular condensation is a poor method for making unsymmetrical ethers such as ethyl methyl ether. Problem-solving Hint Bimolecular condensation of alcohols is generally a poor synthetic method.

Problem 12P Propose a mechanism for the acid-catalyzed condensation of n-propyl alcohol to n-propyl ether, as shown above. When the temperature is allowed to rise too high, propene is formed. Propose a mechanism for the formation of propene, and explain why it is favored at higher temperatures.

Give common names for the following compounds. (a) \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHOCH}\left(\mathrm{CH}_{3}\right) \mathrm{CH}_{2} \mathrm{CH}_{3}\) (b) \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{COCH}_{2} \mathrm{CH}\left(\mathrm{CH}_{3}\right)_{2}\) (c) \(\mathrm{PhOCH}_{2} \mathrm{CH}_{3}\) (d) \(\mathrm{ClCH}_{2} \mathrm{OCH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{3}\) Equation Transcription: Text Transcription: (CH_{3})_{2}CHOCH(CH_{3})CH_{2}CH_{3} (CH_{3})_{3}COCH_{2}CH(CH_{3})_{2} PhOCH_{2}CH_{3} ClCH_{2}OCH_{2}CH_{2}CH_{3} OH OCH_{3} OCH_{3} CH_{3} CH_{3}

Give IUPAC names for the following compounds. (a) \(\mathrm{CH}_{3} \mathrm{OCH}\left(\mathrm{CH}_{3}\right) \mathrm{CH}_{2} \mathrm{OH}\) (b) \(\mathrm{PhOCH}_{2} \mathrm{CH}_{3}\) Equation Transcription: Text Transcription: IUPAC CH_{3}OCH(CH_{3})CH_{2}OH PhOCH_{2}CH_{3} OCH_{3} OCH_{3} OCH_{3} OH CH_{3} OCH_{3} Cl CH_{3}O CH_{2}CH_{3} Br

Problem 34SP (A true story.) An inexperienced graduate student moved into a laboratory and began work. He needed some diethyl ether for a reaction, so he opened an old, rusty 1-gallon can marked “ethyl ether” and found there was half a gallon left. To purify the ether, the student set up a distillation apparatus, started a careful distillation, and went to the stockroom for the other reagents he needed. While he was at the stockroom, the student heard a muffled “boom.” He quickly returned to his lab to find a worker from another laboratory putting out a fire. Most of the distillation apparatus was embedded in the ceiling. (a) Explain what probably happened. (b) Explain how this near-disaster might have been prevented.

Show how you would use a protecting group to convert 4-bromobutan-1-ol to hept-5-yn-1-ol.

Show how you would accomplish the following transformations. Some of these examples require more than one step.

The 2001 Nobel Prize in Chemistry was awarded to three organic chemists who have developed methods for catalytic asymmetric syntheses. An asymmetric (or enantioselective) synthesis is one that converts an achiral starting material into mostly one enantiomer of a chiral product. K. Barry Sharpless (The Scripps Research Institute) developed an asymmetric epoxidation of allylic alcohols that gives excellent chemical yields and greater than 90% enantiomeric excess. The Sharpless epoxidation uses tert-butyl hydroperoxide, titanium(IV) isopropoxide, and a dialkyl tartrate ester as the reagents. The following epoxidation of geraniol is typical. (a) Which of these reagents is most likely to be the actual oxidizing agent? That is, which reagent is reduced in the reaction? What is the likely function of the other reagents? (b) When achiral reagents react to give a chiral product, that product is normally formed as a racemic mixture of enantiomers. How can the Sharpless epoxidation give just one nearly pure enantiomer of the product? (c) Draw the other enantiomer of the product. What reagents would you use if you wanted to epoxidize geraniol to give this other enantiomer? Equation Transcription: Text Transcription: CH_{3} H_{3}C-C-OOH CH_{3} O-Ti-O COOCH_{2}CH_{3} OH HO COOCH_{2}CH_{3}

Problem 41SP Show how you would synthesize the following ethers in good yield from the indicated starting materials and any additional reagents needed. (a) cyclopentyl n-propyl ether from cyclopentanol and propan-1-ol (b) n-butyl phenyl ether from phenol and butan-1-ol (c) 2-ethoxyoctane from an octene (d) 1-methoxydecane from a decene (e) 1-ethoxy-1-methylcyclohexane from 2-methylcyclohexanol (f) trans-2,3-epoxyoctane from octan-2-ol

Problem 42SP There are two different ways of making 2-ethoxyoctane from octan-2-ol using the Williamson ether synthesis. When pure 1-2-octan-2-ol of specific rotation -8.24° is treated with sodium metal and then ethyl iodide, the product is 2-ethoxyoctane with a specific rotation of -15.6o.When pure(-)-octan-2-ol is treated with tosyl chloride and pyridine and then with sodium ethoxide, the product is also 2-ethoxyoctane. Predict the rotation of the 2-ethoxyoctane made using the tosylation/ sodium ethoxide procedure, and propose a detailed mechanism to support your prediction.

(a) When ethylene oxide is treated with anhydrous HBr gas, the major product is 1,2-dibromoethane. When ethylene oxide is treated with concentrated aqueous HBr, the major product is ethylene glycol. Use mechanisms to explain these results. (b) Under base-catalyzed conditions, several molecules of propylene oxide can react to give short polymers. Propose a mechanism for the base-catalyzed formation of the following trimer. Equation Transcription: Text Transcription: HBr HBr 3 H_{2}C-CH-CH_{3} ^{-}OH CH_3 CH_3 CH_3 HO-CH_{2}-CH-O-CH_{2}-CH-O-CH_{2}-CH-OH

Problem 2P Aluminum trichloride (AlCI3) dissolves in ether with the evolution of a large amount of heat. (In fact, this reaction can become rather violent if it gets too warm.) Show the structure of the resulting aluminum chloride etherate complex.

Problem 3P In the presence of 18-crown-6, potassium permanganate dissolves in benzene to give “purple benzene,” a useful reagent for oxidizing alkenes in an aprotic environment. Use a drawing of the complex to show why KMnO4 dissolves in benzene and why the reactivity of the permanganate ion is enhanced.

Problem 22P Propose mechanisms for the epoxidation and ring-opening steps of the epoxidation and hydrolysis of trans-but-2-ene shown above. Predict the product of the same reaction with cis-but-2-ene.

Rank the given solvents in decreasing order of their ability to dissolve each compound. Equation Transcription: Text Transcription: NaOAc OH

Problem 23P Cellosolve® is the trade name for 2-ethoxyethanol, a common industrial solvent. This compound is produced in chemical plants that use ethylene as their only organic feedstock. Show how you would accomplish this industrial process.

Show the rest of the mechanism for formation of the cyclized intermediate in Figure 14-6. Equation Transcription: Text Transcription: HO H_{3}C CH_{3} H_{3}C CH_{3} CH_{3} CH_{3} H_{3}C H_{3}C CH_{3} HO CH_{3} CH_{3} CH_{3} CH_{3} CH_{3} H_{3}C H_{3}C HO

Under the right conditions, the following acid-catalyzed double cyclization proceeds in remarkably good yields. Propose a mechanism. Does this reaction resemble a biological process you have seen? Equation Transcription: Text Transcription: H^+ A^- OH

Problem 45SP Propylene oxide is a chiral molecule. Hydrolysis of propylene oxide gives propylene glycol, another chiral molecule. (a) Draw the enantiomers of propylene oxide. (b) Propose a mechanism for the acid-catalyzed hydrolysis of pure (R)-propylene oxide. (c) Propose a mechanism for the base-catalyzed hydrolysis of pure (R)-propylene oxide. (d) Explain why the acid-catalyzed hydrolysis of optically active propylene oxide gives a product with lower enantiomeric excess and a rotation opposite that of the product of the base-catalyzed hydrolysis

An acid-catalyzed reaction was carried out using methyl cellosolve (2-methoxyethanol) as the solvent. When the 2-methoxyethanol was redistilled, a higher-boiling fraction (bp \(162\ ^{\circ} \mathrm{C}\)) was also recovered. The mass spectrum of this fraction showed the molecular weight to be 134 . The IR and NMR spectra are shown here. Determine the structure of this compound, and propose a mechanism for its formation. Equation Transcription: Text Transcription: 162 ^{o}C NMR (m) (cm^{-1}) CDCl_3 0Hz 50Hz 3.7{delta} 3.6{delta} 3.5{delta} delta(ppm)