The following pseudo-syntheses (guaranteed not to work) exemplify a common conceptual

Classify each reaction as an oxidation, a reduction, or neither. (a) CH3 CH2OH 3 HCCH 3 OHCCH H2CrO4 CrO pyridine 3 (a) O O (b) CH4 CH3OH H C OH H H HO C C OH (b) O O O (c) CH3 C C CH3 H3C CH3 CH3 C C CH3 H2O CH3 OHHO CH3 H+ O + (c) (d) CH3 CH2 OH CH3 CH3 LiAlH4/TiCl4 (d) (e) Br2 H H Br Br (+ enantiomer) (e) (f) H+ C , CH3OH H C H H2O CH3O OCH3 O + (f) (g) (g) HBr H H Br H (h) H2SO4 (H2O) H2 Pt (h) OH (i) OsO4 H2O2 OH OH (i) (j) RCO3H H3O+ O OH OH (+ enantiomer) (j) (k) Cl2 H2O Cl OH (+ enantiomer) (l) (l) (1) BH3 . THF (2) H2O2, OH (k) OH

Predict the products of the reactions of the following compounds with: (1) chromic acid or excess sodium hypochlorite with acetic acid. (2) PCC or NaOCl (1 equivalent) with TEMPO. (a) cyclohexanol (b) 1-methylcyclohexanol (c) cyclopentylmethanol (d) cyclohexanone (e) cyclohexane (f) 1-phenylpropan-1-ol (g) hexan-1-ol (h) acetaldehyde, CH3CHO

We have covered several oxidants that use a multi-valent atom (Cr, Cl, S, or I) as their active species, going from a higher oxidation state before the oxidation to a lower oxidation state after oxidizing the alcohol. Draw the structure of the following atoms, before and after the oxidation of an alcohol to a ketone or aldehyde. How many bonds to oxygen does each atom have before and after the oxidation? (a) the Cr in chromic acid (b) the Cl in sodium hypochlorite (c) the S in the Swern oxidation (d) the I in the DMP reagent (e) the carbinol C in the alcohol that is oxidized

Give the structure of the principal product(s) when each of the following alcohols reacts with (1) Na2Cr2O7>H2SO4, (2) PCC, (3) DMP, and (4) 1 equiv NaOCl-TEMPO. (a) octan-1-ol (b) octan-3-ol (c) 4-hydroxydecanal (d) 1-methylcyclohexan-1,4-diol

Predict the products you expect when the following starting material undergoes oxidation with an excess of each of the reagents shown below. (a) chromic acid (b) PCC (pyridinium chlorochromate) (c) sodium hypochlorite/acetic acid (d) DMSO and oxalyl chloride (e) DMP (periodinane) reagent

Suggest the most appropriate method for each of the following laboratory syntheses. In each case, suggest both a chromium reagent and a chromium-free reagent. (a) \(\text { butan-1-ol } \longrightarrow \text { butanal, } \mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CHO}\) (b) \(\text { but-2-en-1-ol } \longrightarrow \text { but-2-enoic acid, } \mathrm{CH}_{3} \mathrm{CH}=\mathrm{CH}-\mathrm{COOH}\) (c) \(\text { butan-2-ol } \longrightarrow \text { butan-2-one, } \mathrm{CH}_{3} \mathrm{COCH}_{2} \mathrm{CH}_{3}\) (d) cyclopentanol \(\longrightarrow\) 1-ethylcyclopentanol (two steps) (e) cyclopentylmethanol \(\longrightarrow\) 1-cyclopentylpropan-1-ol (two steps) (f) 1-methylcyclohexanol \(\longrightarrow\) 2-methylcyclohexanone (several steps)

A chronic alcoholic requires a much larger dose of ethanol as an antidote to methanol poisoning than does a nonalcoholic patient. Suggest a reason why a larger dose of the competitive inhibitor is required for an alcoholic.

Unlike ethylene glycol, propylene glycol (propane-1,2-diol) is nontoxic because it oxidizes to a common metabolic intermediate. Give the structures of the biological oxidation products of propylene glycol.

Predict the major products of the following reactions. (a) ethyl tosylate + potassium tert-butoxide (b) isobutyl tosylate + NaI (c) (R)-2-hexyl tosylate + NaCN (d) the tosylate of cyclohexylmethanol + excess NH3 (e) n-butyl tosylate + sodium acetylide, HCC:- +Na

Show how you would convert propan-1-ol to the following compounds using tosylate intermediates. You may use whatever additional reagents are needed. (a) 1-bromopropane (b) propan-1-amine, CH3CH2CH2NH2 (c) CH3CH2CH2OCH2CH3 (d) CH3CH2CH2CN ethyl propyl ether butyronitrile

Predict the products of the following reactions. (a) cyclohexylmethanol + TsCl/pyridine (b) product of (a) + \(LiAlH_4\) (c) 1-methylcyclohexanol + \(H_2SO_4\), heat (d) product of (c) + \(H_2\), Pt

Propose a mechanism for the reaction of (a) 1-methylcyclohexanol with HBr to form 1-bromo-1-methylcyclohexane. (b) 2-cyclohexylethanol with HBr to form 1-bromo-2-cyclohexylethane.

The reaction of tert-butyl alcohol with concentrated HCl goes by the \(\mathrm{S}_{\mathrm{N}} 1\) mechanism. Write a mechanism for this reaction.

Show how you would use a simple chemical test to distinguish between the following pairs of compounds. Tell what you would observe with each compound. (a) isopropyl alcohol and tert-butyl alcohol (b) isopropyl alcohol and butan-2-one, \(CH_3COCH_2CH_3\) (c) hexan-1-ol and cyclohexanol (d) allyl alcohol and propan-1-ol (e) butan-2-one and tert-butyl alcohol

Neopentyl alcohol, (CH3)3CCH2OH, reacts with concentrated HBr to give 2-bromo2-methylbutane, a rearranged product. Propose a mechanism for the formation of this product.

Explain the products observed in the following reaction of an alcohol with the Lucas reagent. CH3 HCl/ZnCl2 CH3 H OH CH3 CH3 H Cl CH3 Cl H CH3

When cis-2-methylcyclohexanol reacts with the Lucas reagent, the major product is 1-chloro-1-methylcyclohexane. Propose a mechanism to explain the formation of this product.

Write balanced equations for the three preceding reactions.

Suggest how you would convert trans-4-methylcyclohexanol to (a) trans-1-chloro-4-methylcyclohexane. (b) cis-1-chloro-4-methylcyclohexane.

Two products are observed in the following reaction. D OH SOCl2 D Cl D H Cl + (a) Suggest a mechanism to explain how these two products are formed. (b) Your mechanism for part (a) should be different from the usual mechanism of the reaction of SOCl2 with alcohols. Explain why the reaction follows a different mechanism in this case.

Give the structures of the products you would expect when each alcohol reacts with (1) HCl, ZnCl2; (2) HBr; (3) PBr3; (4) P>I2; and (5) SOCl2. (a) butan-1-ol (b) 2-methylbutan-2-ol (c) 2,2-dimethylbutan-1-ol (d) cis-3-methylcyclopentanol

Predict the products of the sulfuric acid-catalyzed dehydration of the following alcohols. When more than one product is expected, label the major and minor products. (a) 2-methylbutan-2-ol (b) pentan-1-ol (c) pentan-2-ol (d) 1-isopropylcyclohexanol (e) 2-methylcyclohexanol

Some alcohols undergo rearrangement or other unwanted side reactions when they dehydrate in acid. Alcohols may be dehydrated under mildly basic conditions using phosphorus oxychloride (POCl3) in pyridine. The alcohol reacts with phosphorus oxychloride much like it reacts with tosyl chloride (Section 11-5), displacing a chloride ion from phosphorus to give an alkyl dichlorophosphate ester. The dichlorophosphate group is an outstanding leaving group. Pyridine reacts as a base with the dichlorophosphate ester to give an E2 elimination. Propose a mechanism for the dehydration of cyclohexanol by POCl3 in pyridine. N phosphorus oxychloride pyridine

Contrast the mechanisms of the two preceding reactions, the dehydration and condensation of ethanol.

Explain why the acid-catalyzed condensation is a poor method for the synthesis of an unsymmetrical ether such as ethyl methyl ether, CH3CH2OCH3.

Propose a mechanism for each reaction. (a) OH H2SO4 (a) , heat (b) OCH3 H2O H+ O + CH3OH (b) (c) H2SO4 CH , heat 2OH  CH2  (c) (d) CH3CH2OH H+ O CH3 OCH2CH3 HO (a minor product)

When the following substituted cycloheptanol undergoes dehydration, one of the minor products has undergone a ring contraction. Propose a mechanism to show how this ring contraction occurs.

Propose a mechanism for each reaction.

The following reaction involves a starting material with a double bond and a hydroxy group, yet its mechanism resembles a pinacol rearrangement. Propose a mechanism, and point out the part of your mechanism that resembles a pinacol rearrangement.

Predict the products formed by periodic acid cleavage of the following diols. (a) CH3CH(OH)CH(OH)CH3 (b) CH2OH OH (b) (c) CH3 OH CPh CH(OH)CH2CH3 (c) (d) OH H OH H

Show the alcohol and the acid chloride that combine to make the following esters. (a) CH3CH2CH2C OCH2CH2CH3 n-propyl butyrate (a) O (b) n-butyl propionate CH3 CO CH2CH3 (CH2)3 (b) O (c) O H3C O p-tolylisobutyrate C CH(CH3)2 (c) (d) O O C cyclopropyl benzoate

Use resonance forms of the conjugate bases to explain why methanesulfonic acid \((CH_3SO_3H,\ pK_a=-2.6)\) is a much stronger acid than acetic acid \((CH_3COOH,\ pK_a=4.8)\).

A good Williamson synthesis of ethyl methyl ether would be What is wrong with the following proposed synthesis of ethyl methyl ether? First, ethanol is treated with acid to protonate the hydroxy group (making it a good leaving group), and then sodium methoxide is added to displace water.

(a) Show how ethanol and cyclohexanol may be used to synthesize cyclohexyl ethyl ether (tosylation followed by the Williamson ether synthesis). (b) Why can’t we synthesize this product simply by mixing the two alcohols, adding some sulfuric acid, and heating?

A student wanted to use the Williamson ether synthesis to make (R)-2-ethoxybutane. He remembered that the Williamson synthesis involves an SN2 displacement, which takes place with inversion of configuration. He ordered a bottle of (S)-butan-2-ol for his chiral starting material. He also remembered that the SN2 goes best on primary halides and tosylates, so he made ethyl tosylate and sodium (S)-but-2-oxide. After warming these reagents together, he obtained an excellent yield of 2-ethoxybutane. (a) What enantiomer of 2-ethoxybutane did he obtain? Explain how this enantiomer results from the SN2 reaction of ethyl tosylate with sodium (S)-but-2-oxide. (b) What would have been the best synthesis of (R)-2-ethoxybutane? (c) How can this student convert the rest of his bottle of (S)-butan-2-ol to (R)-2-ethoxybutane?

Phenols (pKa 10) are more acidic than other alcohols, so they are easily deprotonated by sodium hydroxide or potassium hydroxide. The anions of phenols (phenoxide ions) can be used in the Williamson ether synthesis, especially with very reactive alkylating reagents such as dimethyl sulfate. Using phenol, dimethyl sulfate, and other necessary reagents, show how you would synthesize methyl phenyl ether.

To practice working through the early parts of a multistep synthesis, devise syntheses of (a) pentan-3-one from alcohols containing no more than three carbon atoms. (b) 3-ethylpentan-2-one from compounds containing no more than three carbon atoms.

Develop syntheses for the following compounds. As starting materials, you may use cyclopentanol, alcohols containing no more than four carbon atoms, and any common reagents and solvents. (a) trans-cyclopentane-1,2-diol (b) 1-chloro-1-ethylcyclopentane (c) O (c) (d) (d) CH3 OCH3 (e) (e) C CH2CH3 OCH2CH3 (f) (f) OCH3

Identify whether oxidation or reduction is needed to interconvert alkanes, alcohols, aldehydes, ketones, and acids, and identify reagents that will accomplish the conversion.

Predict the products of the reactions of alcohols with (a) oxidizing and reducing agents. (b) carboxylic acids and acid chlorides. (c) dehydrating reagents, especially H2SO4 and H3PO4. (d) hydrohalic acids (HCl, HBr, and HI) and the phosphorus halides. (e) sodium metal, potassium metal, and sodium hydride.

Predict the products of the reactions of alkoxide ions.

Use your knowledge of alcohol and diol reactions to propose mechanisms and products for similar reactions that are new. (Problems 11-45, 47, 54, 55, 60, 61, 62, 63, and 65)

Show how to convert an alcohol to a related compound with a different functional group.

Use retrosynthetic analysis to propose single-step and multistep syntheses of compounds using alcohols as starting materials and intermediates. Show how Grignard and organolithium reagents can be used to assemble the carbon skeletons. (Problems 11-42, 46, 48, 56, and 57) Problem-Solving Strategy: Multistep Synthesis (Problems 11-40, 46, 48, 56, and 57)

Predict the major products of the following reactions, including stereochemistry where appropriate. (a) (R)@butan@2@ol + TsCl in pyridine (b) (S)-2-butyl tosylate + NaBr (c) cyclooctanol + NaOCl>HOAc (d) cyclopentylmethanol + CrO3 # pyridine # HCl (e) cyclopentylmethanol + Na2Cr2O7>H2SO4 (f) cyclopentanol + HCl>ZnCl2 (g) n@butanol + HBr (h) cyclooctylmethanol + CH3CH2MgBr (i) potassium tert@butoxide + methyl iodide (j) sodium methoxide + tert@butyl iodide (k) cyclopentanol + H2SO4>heat (l) product from (k) + OsO4>H2O2, then HIO4 (m) sodium ethoxide + 1@bromobutane (n) sodium ethoxide + 2@methyl@2@bromobutane (o) octan-1-ol + DMSO + oxalyl chloride (p) 4-cyclopentylhexan-1-ol + DMP reagent

Show how you would convert 2-methylcyclopentanol to the following products. Any of these products may be used as the reactant in any subsequent part of this problem. (a) 1-methylcyclopentene (b) 2-methylcyclopentyl tosylate (c) 2-methylcyclopentanone (d) 1-methylcyclopentanol (e) 1,2-dimethylcyclopentanol (f) 1-bromo-2-methylcyclopentane (g) 2-methylcyclopentyl acetate (h) 1-bromo-1-methylcyclopentane

In each case, show how you would synthesize the chloride, bromide, and iodide from the corresponding alcohol. (a) 1-halobutane (halo = chloro, bromo, iodo) (b) halocyclopentane (c) 1-halo-1-methylcyclohexane (d) 1-halo-2-methylcyclohexane

Show how you would accomplish the following synthetic conversions.

Predict the major products of dehydration catalyzed by sulfuric acid. (a) hexan-1-ol (b) hexan-2-ol (c) pentan-3-ol (d) 1-methylcyclopentanol (e) cyclopentylmethanol (f) 2-methylcyclopentanol

Predict the esterification products of the following acid/alcohol pairs. (a) CH3CH2CH2COOH + CH3OH (b) CH3OH + HNO3 (c) 2 CH3CH2OH + H3PO4

Both cis- and trans-2-methylcyclohexanol undergo dehydration in warm sulfuric acid to give 1-methylcyclohexene as the major alkene product. These alcohols can also be converted to alkenes by tosylation using TsCl and pyridine, followed by elimination using \(KOC(CH_3)_3\) as a strong base. Under these basic conditions, the tosylate of cis-2-methylcyclohexanol eliminates to give mostly 1-methylcyclohexene, but the tosylate of trans-2-methylcyclohexanol eliminates to give only 3-methylcyclohexene. Explain how this stereochemical difference in reactants controls a regiochemical difference in the products of the basic elimination, but not in the acid-catalyzed elimination.

Show how you would convert (S)-hexan-2-ol to (a) (S)-2-chlorohexane. (b) (R)-2-bromohexane. (c) (R)-hexan-2-ol.

When 1-cyclohexylethanol is treated with concentrated aqueous HBr, the major product is 1-bromo-1-ethylcyclohexane. (a) Propose a mechanism for this reaction. (b) How would you convert 1-cyclohexylethanol to (1-bromoethyl)cyclohexane in good yield?

Show how you would make each compound, beginning with an alcohol of your choice.

Predict the major products (including stereochemistry) when cis-3-methylcyclohexanol reacts with the following reagents. (a) PBr3 (b) SOCl2 (c) Lucas reagent (d) concentrated HBr (e) TsCl/pyridine, then NaBr

Show how you would use simple chemical tests to distinguish between the following pairs of compounds. In each case, describe what you would do and what you would observe. (a) butan-1-ol and butan-2-ol (b) butan-2-ol and 2-methylbutan-2-ol (c) cyclohexanol and cyclohexene (d) cyclohexanol and cyclohexanone (e) cyclohexanone and 1-methylcyclohexanol

The compound shown below has three different types of OH groups, all with different acidities. Show the structure produced after this compound is treated with different amounts of NaH followed by a methylating reagent. Add a brief explanation. (a) 1 equivalent of NaH, followed by 1 equivalent of CH3I and heat (b) 2 equivalents of NaH, followed by 2 equivalents of CH3I and heat (c) 3 equivalents of NaH, followed by 3 equivalents of CH3I and heat

Compound A is an optically active alcohol. Treatment with chromic acid converts A into a ketone, B. In a separate reaction, A is treated with PBr3, converting A into compound C. Compound C is purified, and then it is allowed to react with magnesium in ether to give a Grignard reagent, D. Compound B is added to the resulting solution of the Grignard reagent. After hydrolysis of the initial product (E), this solution is found to contain 3,4-dimethylhexan-3-ol. Propose structures for compounds A, B, C, D, and E.

Give the structures of the intermediates and products V through Z.

Under acid catalysis, tetrahydrofurfuryl alcohol reacts to give surprisingly good yields of dihydropyran. Propose a mechanism to explain this useful synthesis.

Propose mechanisms for the following reactions. In most cases, more products are formed than are shown here. You only need to explain the formation of the products shown, however.

Show how you would synthesize the following compounds. As starting materials, you may use any alcohols containing four or fewer carbon atoms, cyclohexanol, and any necessary solvents and inorganic reagents.

Show how you would synthesize the following compound. As starting materials, you may use any alcohols containing five or fewer carbon atoms and any necessary solvents and inorganic reagents.

The following pseudo-syntheses (guaranteed not to work) exemplify a common conceptual error. (a) What is the conceptual error implicit in these syntheses? (b) Propose syntheses that are more likely to succeed.

Two unknowns, X and Y, both having the molecular formula C4H8O, give the following results with four chemical tests. Propose structures for X and Y consistent with this information. Bromine Na Metal Chromic Acid Lucas Reagent Compound X decolorizes bubbles orange to green no reaction Compound Y no reaction no reaction no reaction no reaction

The Williamson ether synthesis involves the displacement of an alkyl halide or tosylate by an alkoxide ion. Would the synthesis shown be possible by making a tosylate and displacing it? If so, show the sequence of reactions. If not, explain why not and show an alternative synthesis that would be more likely to work.

Chromic acid oxidation of an alcohol (Section 11-2A) occurs in two steps: formation of the chromate ester, followed by an elimination of H+ and chromium. Which step do you expect to be rate-limiting? Careful kinetic studies have shown that Compound A undergoes chromic acid oxidation over 10 times as fast as Compound B. Explain this large difference in rates.

(a) The reaction of butan-2-ol with concentrated aqueous HBr goes with partial racemization, giving more inversion than retention of configuration. Propose a mechanism that accounts for racemization with excess inversion. (b) Under the same conditions, an optically active sample of trans-2-bromocyclopentanol reacts with concentrated aqueous HBr to give an optically inactive product, (racemic) trans-1,2-dibromocyclopentane. Propose a mechanism to show how this reaction goes with apparently complete retention of configuration, yet with racemization. (Hint: Draw out the mechanism of the reaction of cyclopentene with Br2 in water to give the starting material, trans-2- bromocyclopentanol. Consider how parts of this mechanism might be involved in the reaction with HBr.)

Alcohols combine with ketones and aldehydes to form interesting derivatives, which we will discuss in Chapter 18. The following reactions show the hydrolysis of two such derivatives. Propose mechanisms for these reactions.

Unknown Q is determined to have a molecular formula of \(C_6H_{12}O\). Q is not optically active, and passing it through a chiral column does not separate it into enantiomers. Q does not react with \(Br_2\), nor with cold, dilute \(KMnO_4\), nor does it take up \(H_2\) under catalytic hydrogenation. Heating of Q with \(H_2SO_4\) gives product R, of formula \(C_6H_{10}\), which can be separated into enantiomers. Ozonolysis of a single enantiomer of R produces S, an acyclic, optically active ketoaldehyde of formula \(C_6H_{10}O_2\). Propose structures for compounds Q, R, and S, and show how your structures would react appropriately to give these results.

Trichloroisocyanuric acid, TCICA, also known as swimming pool chlorine, is a stable solid that oxidizes alcohols, following a mechanism similar to oxidation by HOCl. No reaction occurs between TCICA and the alcohol (in a solvent such as acetonitrile) until one drop of HCl(aq) is added, whereupon the reaction is over in a few minutes. Write the mechanism for this oxidation that shows the key role of the acid catalyst. Show the oxidation of just one alcohol, not three. (Hint: The carbonyls are the most basic sites on TCICA.)

Under normal circumstances, tertiary alcohols are not oxidized. However, when the tertiary alcohol is allylic, it can undergo a migration of the double bond (called an allylic shift) and subsequent oxidation of the alcohol. A particularly effective reagent for this reaction is Bobbitt’s reagent, similar to TEMPO used in many oxidations. (M. Shibuya et al., J. Org. Chem., 2008, 73, 4750.) Show the expected product when each of these \(3^{\circ}\) allylic alcohols is oxidized by Bobbitt’s reagent.