Fill in each box with the appropriate reagent:

Draw the product of each of the following reactions:

Indicate which alcohol in each pair will undergo an elimination reaction more rapidly when heated with H 2 SO 4 .

Identify A E.

Starting with ( R )-1-deuterio-1-propanol, how could you prepare a. ( S )-1-deuterio-1-propanol? b. ( S )-1-deuterio-1-methoxypropane? c. ( R )-1-deuterio-1-methoxypropane?

Write the appropriate reagent over each arrow.

What alkenes would you expect to be obtained from the acid-catalyzed dehydration of 1-hexanol?

Draw the major product(s) of each of the following reactions:

When heated with H 2 SO 4 , both 3,3-dimethyl-2-butanol and 2,3-dimethyl-2-butanol are dehydrated to form 2,3-dimethyl-2-butene. Which alcohol dehydrates more rapidly?

What is the major product obtained from the reaction of 2-ethyloxirane with each of the following reagents? a. 0.1 M HCl b. CH3OH>HCl c. 0.1 M NaOH d. CH3OH>CH3O -

When deuterated phenanthrene oxide undergoes a rearrangement in water to form a phenol, 81% of the deuterium is retained in the product. H D O a. What percentage of the deuterium will be retained if an NIH shift occurs? b. What percentage of the deuterium will be retained if an NIH shift does not occur?

An unknown alcohol with a molecular formula of C 7 H 14 O was oxidized to an aldehyde with HOCl. When an acidic solution of the alcohol was distilled, two alkenes were formed. The alkene formed in greater yield was determined to be 1-methylcyclohexene. The other alkene formed the original unknown alcohol when treated with BH 3 /THF followed by H 2 O 2 , HO , H 2 O. Identify the unknown alcohol

Fill in each box with the appropriate reagent:

Explain why ( S )-2-butanol forms a racemic mixture when it is heated in sulfuric acid.

Propose a mechanism for the following reaction:

What product would be formed if the four-membered ring alcohol in Problem 61 were heated with an equivalent amount of HBr rather than with a catalytic amount of H 2 SO 4 ?

Which of the following ethers would be obtained in greatest yield directly from alcohols?

Using the given starting material, any necessary inorganic reagents, and any carbon-containing compounds with no more than two carbons, indicate how the following syntheses could be carried out:

When piperidine undergoes the series of reactions shown here, 1,4-pentadiene is obtained as the product. When the four different methyl-substituted piperidines undergo the same series of reactions, each forms a different diene: 1,5-hexadiene, 1,4-pentadiene, 2-methyl-1,4-pentadiene, and 3-methyl- 1,4-pentadiene. Which methyl-substituted piperidine forms which diene?

When 3-methyl-2-butanol is heated with concentrated HBr, a rearranged product is obtained. When 2- methyl-1-propanol reacts under the same conditions, a rearranged product is not obtained. Explain.

Propose a mechanism for each of the following reactions:

How could you synthesize isopropyl propyl ether, using isopropyl alcohol as the only carbon- containing reagent?

When the following seven-membered ring alcohol is dehydrated, three alkenes are formed. Propose a mechanism for their formation.

Ethylene oxide reacts readily with \(HO^{-}\) because of the strain in the three-membered ring. Explain why cyclopropane, a compound with approximately the same amount of strain, does not react with \(HO^{-}\).

The Swern oxidation oxidizes primary alcohols to aldehydes and secondary alcohols to ketones using dimethyl sulfoxide and oxalyl chloride, followed by reaction with triethylamine. The actual oxidizing agent is the dimethylchlorosulfonium ion, (CH 3 ) 2S + Cl. (To see how this compound is formed from the reactants, see Problem 77 in Chapter 17 .) Propose a mechanism for the oxidation. ( Hint: the i rst step is an S N 2 reaction, the last step is an E2 reaction.)

Propose a mechanism for each of the following reactions

Explain why the acid-catalyzed dehydration of an alcohol is a reversible reaction, whereas the base- promoted dehydrohalogenation of an alkyl halide is an irreversible reaction.

Triethylene glycol is one of the products obtained from the reaction of ethylene oxide and hydroxide ion. Propose a mechanism for its formation.

a. Propose a mechanism for the following reaction: CH2CH2CH2Br Br O CH2OCH3 + CH3O O b. A small amount of a product containing a six-membered ring is also formed. Draw the structure of that product. c. Why is so little six-membered ring product formed?

Propose a mechanism for the following reaction:

When ethyl ether is heated with excess HI for several hours, the only organic product obtained is ethyl iodide. Explain why ethyl alcohol is not obtained as a product.

Propose a mechanism for the following reaction:

Early organic chemists used the Hofmann elimination reaction as the last step of a process known as a Hofmann degradationa method used to identify amines. In a Hofmann degradation, an amine is methylated with excess methyl iodide in a basic solution, treated with silver oxide to convert the quaternary ammonium iodide to a quaternary ammonium hydroxide, and then heated to allow it to undergo a Hofmann elimination. Once the alkene product is identii ed, working backward gives the structure of the amine. Identify the amine in each of the following cases: a. 4-Methyl-2-pentene is obtained from the Hofmann degradation of a primary amine. b. 3-Methyl-1-butene is obtained from the Hofmann degradation of a primary amine. c. 2-Methyl-1-3-butadiene is obtained from two successive Hofmann degradations of a secondary amine.

An ion with a positively charged nitrogen atom in a three-membered ring is called an aziridinium ion. The following aziridinium ion reacts with sodium methoxide to form compounds A and B: N + C C CH3 an aziridinium ion H3C H3C CH3 H3C CH3 If a small amount of aqueous Br 2 is added to A, the reddish color of Br 2 persists, but the color disappears when Br 2 is added to B. When the aziridinium ion reacts with methanol, only A is formed. Identify A and B

Propose a mechanism for each of the following reactions:

Which of the following reactions occurs most rapidly? Why?

The following reaction takes place several times faster than the reaction of 2-chlorobutane with HO- . (CH3CH2 )2N CH2CHCH2CH3 Cl (CH3CH2 )2N CHCH2CH3 CH2OH HO a. Explain the enhanced reaction rate. b. Explain why the OH group in the product is not bonded to the carbon that was bonded to the Cl group in the reactant

A vicinal diol has OH groups on adjacent carbons. The dehydration of a vicinal diol is accompanied by a rearrangement called the pinacol rearrangement. Propose a mechanism for this reaction. CH3 C OH CH3 C OH CH3 CH3 CH3 C CH3 O CH3 C CH3 H2O

hough 2-methyl-1,2-propanediol is an unsymmetrical vicinal diol, only one product is obtained when it is dehydrated in an acidic solution. a. What is this product? b. Why is only one product obtained?

What product is obtained when the following vicinal diol is heated in an acidic solution? OH HO

Two stereoisomers are obtained from the reaction of cyclopentene oxide and dimethylamine. The R,R -isomer is used in the manufacture of eclanamine, an antidepressant. What other isomer is obtained?

Propose a mechanism for each of the following reactions:

Triethylenemelamine (TEM) is an antitumor agent. Its activity is due to its ability to cross-link DNA. a. Explain why it can be used only under slightly acidic conditions. b. Explain why it can cross-link DNA.

Problem 1P Why are NH3 and CH3NH2 no longer nucleophiles when they are“pfotonated?

Problem 2P The observed relative reactivities of primary, secondary, and tertiary alcohols with a hydrogen halide are 3o > 2o > 7o. If secondary alcohols were to undergo an SN2 reaction rather than an SN1 reaction with a hydrogen halide, what would be the relative reactivities of the three classes of alcohols?

Show how \(1-\text{butanol}\) can be converted into the following compounds: Equation Transcription: 1-butanol Text Transcription: 1-butanol

Using the \(\mathrm{pK}_\mathrm{a}\) values of the conjugate acids of the leaving groups (the \(\mathrm{pK}_\mathrm{a}\) of \(\mathrm{HBr}\) is \(?9\), the \(\mathrm{pK}_\mathrm{a}\) of \(\mathrm{H}_2\mathrm{O}\) is \(15.7\), and the \(\mathrm{pK}_\mathrm{a}\) of \(\mathrm{H}_3\mathrm{O}^+\) is \(?1.7\)), explain the difference in reactivity in substitution reactions between Equation Transcription: pKa HBr ?9 H2O 15.7 H3O+ ?1.7 Text Transcription: pK_a HBr -9 H_2 0 15.7 H_3 O^+ -1.7

What is the major product of each of the following reactions?

What stereoisomers would be obtained from the following reactions?

What stereoisomers would be formed from the following reactions?

What stereoisomers would be obtained from the following reactions?

Show how \(1-\text{propanol}\) can be converted into the following compounds by means of a sulfonate ester: Equation Transcription: 1-propanol Text Transcription: 1-propanol

Which of the following alcohols would dehydrate the fastest when heated with acid?

Draw the major product obtained when each of the following alcohols is heated in the presence of \(\mathrm{H}_2\mathrm{SO}_4\): Equation Transcription: H2SO4 Text Transcription: H_2 SO_4

Problem 13P Heating an alcohol with H2SO4 is a good way to prepare a symmetrical ether such as diethyl ether. a. Explain why it is not a good way to prepare an unsymmetrical ether such as ethyl propyl ether. ________________ b. How would you synthesize ethyl propyl ether?

Propose a mechanism for each of the following reactions:

Draw the product of each of the following reactions:

Explain why the following alcohols, when heated with acid, form the same alkene.

Problem 17P What stereoisomers are formed in the following reactions? Which stereoisomer is the major product? a. the acid-catalyzed dehydration of 1-pentanol to 2-pentene b. the acid-catalyzed dehydration of 3,4-dimethyl-3-hexanol to 3,4-dimethyl-3-hexene

Suppose the following compound is heated in the presence of \(\mathrm{H}_2\mathrm{SO}_4\). a. What constitutional isomer is produced in greatest yield? b. What stereoisomer is produced in greater yield? Equation Transcription: H2SO4 Text Transcription: H_2 SO_4

What alcohol would you treat with phosphorus oxychloride and pyridine to form each of the following alkenes?

Problem 20P What product will be obtained from the reaction of each of the following alcohols with HOCl? a. 3-pentanol c. 2-methyl-2-pentanol e. cyclohexanol b. 1-pentanol d. 2,4-hexanediol f. 1,4-butanediol

Problem 22P Can HF be used to cleave ethers? Explain.

Draw the major products obtained from heating each of the following ethers with one equivalent of \(\text{HI}\): Equation Transcription: HI Text Transcription: HI

Draw the major product of each of the following reactions:

Problem 25P Would you expect the reactivity of a five-mcmbcred ring ether such as tetrahydrofuran (Table) to be more similar to an epoxide or to a noncyclic ether?

Problem 26P How could the following compounds be prepared from 3,3-dimethyl-1-butene? a. 2,3-dimethyl-2-butanol b. 3,3-dimethyl-2-butanol

Problem 27P What products would be obtained from the reaction of cyclohexene oxide with a. methoxide ion? b. methylamine?

What products would be formed from the reaction of each of the following alkenes with \(\mathrm{OsO}_4\) followed by aqueous \(\mathrm{H}_2\mathrm{O}_2\)? Equation Transcription: OsO4 H2O2 Text Transcription: OsO_4 H_2 O_2

Problem 29P What stereoisomers would be obtained from the reaction of each of the following alkenes with OsO4 followed by aqueous H2O2? a. Trans-2-butene b. cis-2-butene c. cis-2-pentene d. trans-2-pentene

Problem 30P What stereoisomers would be obtained from the reaction of the alkenes in Problem 29 with a peroxyacid followed by reaction with hydroxide ion? What stereoisomers would be obtained from the reaction of each of the following alkenes with OsO4 followed by aqueous H2O2? a. trans-2-butene b. cis-2-butene c. cis-2-pentene d. trans-2-pentene

Problem 31P Draw all possible resonance contributors for the two carbocations in the preceding reaction. Use the resonance contributors to explain why 1-naphthol is the major product of the reaction.

The existence of the \(\mathrm{NIH}\) shift was established by determining the major product obtained from rearrangement of the following arene oxide, in which a hydrogen has been replaced by a deuterium. a. What would be the major product if the \(\mathrm{NIH}\) shift occurs? (Hint: A \(\mathrm{C} ? \mathrm{H}\) bond is easier to break than a \(\mathrm{C} ? \mathrm{D}\) bond.) b. What would be the major product if the carbocation forms phenol by losing a proton, rather than by going through the \(\mathrm{NIH}\) shift? Equation Transcription: NIH C ? H C ? D Text Transcription: NIH C ? H C ? D

How would the major products obtained from rearrangement of the following arene oxides differ?

Which compound in each pair is more likely to be carcinogenic?

Explain why the two arene oxides in \(\text{Problem} \ 34\mathrm{a}\) open in opposite directions. Equation Transcription: Problem 34a Text Transcription: Problem 34a

Three arene oxides can be obtained from phenanthrene. a. Draw the structures of the three phenanthrene oxides. b. Draw the structures of the phenols that can be obtained from each phenanthrene oxide. c. If a phenanthrene oxide can lead to the formation of more than one phenol, which phenol will be obtained in greater yield? d. Which of the three phenanthrene oxides is most likely to be carcinogenic?

Problem 37P Explain why the half-life (the time it takes for one-half of the compound to be metabolized) of Xylocaine is longer than that of Novocaine.

If a quarternary ammonium ion can undergo an elimination reaction with a strong base, why can’t a protonated tertiary amine undergo the same reaction?

What are the major products of the following reaction?

Problem 40P What are the minor products of the preceding Hofmann elimination reaction?

Problem 41P What is the difference between the reaction that occurs when isopropyltrimethylammonium hydroxide is heated and the reaction that occurs when 2-bromopropane is treated with hydroxide ion?

What is the major product of each of the following reactions?

Describe a synthesis for each of the following compounds, using the given starting material and any necessary reagents:

Using an alkyl halide and a thiol as starting materials, how would you prepare the following thioethers?

The following three nitrogen mustards were studied for possible clinical use. One is now used clinically, one was found to be too unreactive, and one was found to be too insoluble in water to be injected intravenously. Which is which? (Hint: Draw resonance contributors.)

Problem 46P Why is melphalan a good cancer drug?

Mechlorethamine, the drug in \(\text{Problem} \ 45\) that is in clinical use, is highly reactive so can be administered only by physicians who are experienced in its use. Explain why cyclophosphamide, carmustine, and chloroambucil are less reactive alkylating agents. Equation Transcription: Problem 45 Text Transcription: Problem 45

Indicate which alcohol in each pair will undergo an elimination reaction more rapidly when heated with \(\mathrm{H}_2\mathrm{SO}_4\). Equation Transcription: H2SO4 Text Transcription: H_2 SO_4

Identify \(\mathrm{A} – \mathrm{E}\). Equation Transcription: A – E Text Transcription: A – E

Problem 51P Starting with (R)-1-deuterio-1-propanol, how could you prepare a. (S)-1-deuterio-1-propanol? b. (S)-1-deuterio-1-methoxypropane? c. (R)-1-deuterio-1-methoxypropane?

What alkenes would you expect to be obtained from the acid-catalyzed dehydration of 1-hexanol?

Write the appropriate reagent over each arrow.

Problem 55P When heated with H2SO4, both 3,3-dimethyl-2-butanol and 2,3-dimethyl-2-butanol are dehydrated to form 2,3-dimethyl-2-butene. Which alcohol dehydrates more rapidly?

Problem 56P What is the major product obtained from the reaction of 2-ethyloxirane with each of the following reagents? a. 0.1 M HCl b. CH3OH/HCl c. 0.1 M NaOH d. CH3OH/CH3O-

When deuterated phenanthrene oxide undergoes a rearrangement in water to form a phenol, \(81\%\) of the deuterium is retained in the product. a. What percentage of the deuterium will be retained if an \(\mathrm{NIH}\) shift occurs? b. What percentage of the deuterium will be retained if an \(\mathrm{NIH}\) shift does not occur? Equation Transcription: 81% NIH Text Transcription: 81% NIH

Problem 58P An unknown alcohol with a molecular formula of C7H14O was oxidized to an aldehyde with HOCl. When an acidic solution of the alcohol was distilled, two alkenes were formed. The alkene formed in greater yield was determined to be 1-methylcyclohexene. The other alkene formed the original unknown alcohol when treated with BH3/THF followed by H2O2, HO–, H2O. Identify the unknown alcohol.

Fill in each box with the appropriate reagent:

Problem 60P Explain why (S)-2-butanol forms a racemic mixture when it is heated in sulfuric acid.

Propose a mechanism for the following reaction:

What product would be formed if the four-membered ring alcohol in \(\text{Problem} \ 61\) were heated with an equivalent amount of \(\mathrm{HBr}\) rather than with a catalytic amount of \(\mathrm{H}_2\mathrm{SO}_4\)? Equation Transcription: Problem 61 HBr H2SO4 Text Transcription: Problem 61 HBr H_2 SO_4

Which of the following ethers would be obtained in greatest yield directly from alcohols?

Using the given starting material, any necessary inorganic reagents, and any carbon-containing compounds with no more than two carbons, indicate how the following syntheses could be carried out:

When piperidine undergoes the series of reactions shown here, \(1,4-\text{pentadiene}\) is obtained as the product. When the four different methyl-substituted piperidines undergo the same series of reactions, each forms a different diene: \(1,5-\text{hexadiene}\), \(1,4-\text{pentadiene}\), \(2-\text{methyl}-1,4-\text{pentadiene}\), and \(3-\text{methyl}-1,4-\text{pentadiene}\). Which methyl-substituted piperidine forms which diene? Equation Transcription: 1,4-pentadiene 1,5-hexadiene 2-methyl-1,4-pentadiene 3-methyl-1,4-pentadiene Text Transcription: 1,4-pentadiene 1,5-hexadiene 2-methyl-1,4-pentadiene 3-methyl-1,4-pentadiene

Problem 66P When 3-methyl-2-butanol is heated with concentrated HBr, a rearranged product is obtained. When 2-methyl-1-propanol reacts under the same conditions, a rearranged product is not obtained. Explain.

Propose a mechanism for each of the following reactions:

Problem 68P How could you synthesize isopropyl propyl ether, using isopropyl alcohol as the only carbon-containing reagent?

When the following seven-membered ring alcohol is dehydrated, three alkenes are formed. Propose a mechanism for their formation.

Ethylene oxide reacts readily with \(HO^?\) because of the strain in the three-membered ring. Explain why cyclopropane, with approximately the same amount of strain, does not react with \(HO^?\).

The Swern oxidation oxidizes primary alcohols to aldehydes and secondary alcohols to ketones using dimethyl sulfoxide and oxalyl chloride, followed by reaction with triethylamine. The actual oxidizing agent is the dimethylchlorosulfonium ion, (\(\mathrm{CH}_3)_2\mathrm{SCl}\). (To see how this compound is formed from the reactants, see \(\text{Problem} \ 77\) in \(\text{Chapter} \ 17\).) Propose a mechanism for the oxidation. (Hint: the first step is an \(\mathrm{S}_\mathrm{N}2\) reaction, the last step is an \(\mathrm{E}2\) reaction.) Equation Transcription: (CH3)2SCI Problem 77 Chapter 17 SN2 E2 Text Transcription: (CH_3)_2 SCI Problem 77 Chapter 17 S_N 2 E2

Propose a mechanism for each of the following reactions:

Problem 73P Explain why the acid-catalyzed dehydration of an alcohol is a reversible reaction, whereas the base promoted dehydrohalogenation of an alkyl halide is an irreversible reaction.

Triethylene glycol is one of the products obtained from the reaction of ethylene oxide and hydroxide ion. Propose a mechanism for its formation.

a. Propose a mechanism for the following reaction: b. A small amount of a product containing a six-membered ring is also formed. Draw the structure of that product. c. Why is so little six-membered ring product formed?

Propose a mechanism for the following reaction:

Problem 77P When ethyl ether is heated with excess HI for several hours, the only organic product obtained is ethyl iodide. Explain why ethyl alcohol is not obtained as a product.

Propose a mechanism for the following reaction:

Problem 79P Early organic chemists used the Hofmann elimination reaction as the last step of a process known as a Hofmann degradation—a method used to identify amines. In a Hofmann degradation, an amine is methylated with excess methyl iodide in a basic solution, treated with silver oxide to convert the quaternary ammonium iodide to a quaternary ammonium hydroxide, and then heated to allow it to undergo a Hofmann elimination. Once the alkene product is identified, working backward gives the structure of the amine. Identify the amine in each of the following cases: a. 4-Methyl-2-pentene is obtained from the Hofmann degradation of a primary amine. b. 3-Methyl-1-butene is obtained from the Hofmann degradation of a primary amine. c. 2-Methyl-1-3-butadiene is obtained from two successive Hofmann degradations of a secondary amine.

An ion with a positively charged nitrogen atom in a three-membered ring is called an aziridinium ion. The following aziridinium ion reacts with sodium methoxide to form compounds \(\mathrm{A}\) and \(\mathrm{B}\): If a small amount of aqueous \(\mathrm{Br}_2\) is added to \(\mathrm{A}\), the reddish color of \(\mathrm{Br}_2\) persists, but the color disappears when \(\mathrm{Br}_2\) is added to \(\mathrm{B}\). When the aziridinium ion reacts with methanol, only \(\mathrm{A}\) is formed. Identify \(\mathrm{A}\) and \(\mathrm{B}\). Equation Transcription: A B Br2 Text Transcription: A B Br_2

Propose a mechanism for each of the following reactions:

Which of the following reactions occurs most rapidly? Why?

The following reaction takes place several times faster than the reaction of \(2-\text{chlorobutane}\) with \(\mathrm{HO}^-\). a. Explain the enhanced reaction rate. b. Explain why the \(\mathrm{OH}\) group in the product is not bonded to the carbon that was bonded to the \(\mathrm{Cl}\) group in the reactant. Equation Transcription: 2-chlorobutane HO? OH Cl Text Transcription: 2-chlorobutane HO^- OH Cl

A vicinal diol has \(\mathrm{OH}\) groups on adjacent carbons. The dehydration of a vicinal diol is accompanied by a rearrangement called the pinacol rearrangement. Propose a mechanism for this reaction. Equation Transcription: OH Text Transcription: OH

Problem 85P Although 2-methyl-1,2-propanediol is an unsymmetrical vicinal diol, only one product is obtained when it is dehydrated in an acidic solution. a. What is this product? b. Why is only one product obtained?

What product is obtained when the following vicinal diol is heated in an acidic solution?

Two stereoisomers are obtained from the reaction of cyclopentene oxide and dimethylamine. The \(R, R\)-isomer is used in the manufacture of eclanamine, an antidepressant. What other isomer is obtained? Equation Transcription: Text Transcription: R, R

Propose a mechanism for each of the following reactions:

Triethylenemelamine (\(T E M\)) is an antitumor agent. Its activity is due to its ability to cross-link DNA. a. Explain why it can be used only under slightly acidic conditions. b. Explain why it can cross-link DNA. Equation Transcription: Text Transcription: TEM