Alcohols and Phenols

Give IUPAC names for the following compounds:

Draw structures corresponding to the following IUPAC names:

1. (Z)-2-Ethyl-2-buten-1-ol
2. 3-Cyclohexen-1-ol
3. trans-3-Chlorocycloheptanol
4. 1,4-Pentanediol
5. 2,6-Dimethylphenol
6. o-(2-Hydroxyethyl)phenol

The following data for isomeric four-carbon alcohols show that there is a decrease in boiling point with increasing substitution of the OH-bearing carbon. How might you account for this trend?

1-Butanol, bp  $\mathbf{117}\mathbf{.}{\mathbf{5}}^o\mathbf{C}$

2-Butanol, bp  $\mathbf{99}\mathbf{.}{\mathbf{5}}^o\mathbf{C}$

2-Methyl-2-propanol, bp  $\mathbf{82}\mathbf{.}{\mathbf{2}}^o\mathbf{C}$

Rank the following substances in order of increasing acidity:

1. (CH₃)₂CHOH, $\mathrm{HC}\equiv \mathrm{CH}$, (CF₃)₂CHOH, CH₃OH
2. Phenol, p-methyl phenol, p-(trifluoromethyl)phenol
3. Benzyl alcohol, phenol, p-hydroxybenzoic acid

p-Nitrobenzyl alcohol is more acidic than benzyl alcohol, but p-methoxy-benzyl alcohol is less acidic. Explain.

Show the products obtained from addition of methylmagnesium bromide to the following compounds:

1. Cyclopentanone
2. Benzophenone (diphenyl ketone)
3. 3-Hexanone

Question: Predict the products of the following reactions:

(a) 

(b) 

(c) 

Question: What reagent would you use to accomplish each of the following reactions?

(a) 

(b)

(c)

Question: What carbonyl compounds give the following alcohols on reduction with ? Show all possibilities.

(a)

(b)

(c)

(d) ${\left({\mathbf{CH}}_{\mathbf{3}}\right)}_{\mathbf{2}}{\mathbf{CHCH}}_{\mathbf{2}}\mathbf{OH}$

Question: Use a Grignard reaction to prepare the following alcohols.

1. 2-Methyl-2-propanol
2. 1-Methylcyclohexanol
3. 3-Methyl-3-pentanol
4. 2-Phenyl-2-butanol
5. Benzyl alcohol
6. 4-Methyl-1-pentanol

Use the reaction of a Grignard reagent with a carbonyl compound to synthesize the following compound:

How would you carry out the following transformation, a step used in the commercial synthesis of (S)-ibuprofen?

What product (s) would you expect from dehydration of the following alcohols with ${\mathbf{POCl}}_3$ in pyridine? Indicate the major product in each case.

(a) 

(b) 

(C) 

(d) 

(e) 

What alcohols would give the following products on oxidation?

(a)  

(b) 

(c) 

What products would you expect from oxidation of the following compounds with ${\mathbf{CrO}}_3$  in aqueous acid? With the Dess-Martin periodinane?

1. 1-Hexanol
2. 2-Hexanol
3. Hexanal

TMS ethers can be removed by treatment with fluoride ion as well as by acid-catalyzed hydrolysis. Propose a mechanism for the reaction of cyclohexyl TMS ether with LiF. Fluorotrimethylsilane is a product.

Show the mechanism for the reaction of p-methylphenol with 2-methylpropene and ${\mathbf{H}}_3{\mathbf{PO}}_4$ catalyst to yield the food additive BHT.

Assume that you need to prepare 5-Cholesten-3-one from Cholesterol. How could you use IR spectroscopy to tell whether the reaction was successful? What differences would you look for in the IR spectra of starting material and product?

When the  ${}^{\mathbf{1}}\mathbf{H}$NMR spectrum of an alcohol is run in dimethyl sulfoxide (DMSO) solvent rather than in chloroform, exchange of the O-H proton is slow and spin-spin splitting is seen between the O-H proton and C-H protons on the adjacent carbon. What spin multiplicities would you expect for the hydroxyl protons in the following alcohols?

1. 2-Methyl-2-propanol
2. Cyclohexanol
3. Ethanol
4. 2-Propanol
5. Cholesterol
6. 1-Methylcyclohexanol

What products would you obtain from reaction of 1-pentanol with the

following reagents?

(a) ${\mathbf{PBr}}_{\mathbf{3}}$

(b)${\mathbf{SOCl}}_{\mathbf{2}}$ 

(c) ${\mathbf{CrO}}_{\mathbf{3}}$ , ${\mathbf{H}}_{\mathbf{2}}\mathbf{O}$ ,${\mathbf{H}}_{\mathbf{2}}{\mathbf{SO}}_{\mathbf{4}}$

(d) Dess–Martin periodinane

Question: How would you prepare the following compounds from

2-phenylethanol?

More than one step may be required.

(a) Styrene$\left(\mathbf{PhCH}\mathbf{=}{\mathbf{CH}}_{\mathbf{2}}\right)$ 

(b) Phenylacetaldehyde$\left({\mathbf{PhCH}}_{\mathbf{2}}\mathbf{CHO}\right)$ 

(c) Phenylacetic acid$\left({\mathbf{PhCH}}_{\mathbf{2}}{\mathbf{CO}}_{\mathbf{2}}\mathbf{H}\right)$

(d) Benzoic acid

(e) Ethylbenzene

(f) Benzaldehyde

(g) 1-Phenylethanol

(h) 1-Bromo-2-phenylethane

Propose a structure for a compound ${\mathbf{C}}_{\mathbf{15}}{\mathbf{H}}_{\mathbf{24}}\mathbf{O}$ that has the following ${}^{\mathbf{1}}\mathbf{H}$NMR spectrum. The peak marked by an asterisk disappears when ${\mathbf{D}}_{\mathbf{2}}\mathbf{O}$ is added to the sample.

How would you carry out the following transformations?

(a)

(b)

(c)

Benzoquinone is an excellent dienophile in the Diels – Alder reaction. What product would you expect from reaction of benzoquinone with 1 equivalent of 1,3 butadiene? From reaction with 2 equivalents of 1,3 butadiene?

Draw and name the eight isomeric alcohols with formula ${\mathbf{C}}_{\mathbf{5}}{\mathbf{H}}_{\mathbf{12}}\mathbf{O}\mathbf{ }\mathbf{ }$

Which of the eight alcohols that you identified in Problem 17-38 react with ${\mathbf{CrO}}_{\mathbf{3}}$ in aqueous acid? Show the products you would expect from each reaction

Rank the following substituted phenol in the increasing order of acidity, and explain your answer:

Benzyl chloride can be converted intobenzaldehyde by treatment with nitromethane and base. The reactioninvolves the initial conversion of nitromethane in to its anion, followed by SN2 reaction of the anion with benzyl chloride and subsequent E2 reaction. Write the mechanism in detail, using curved arrows to indicate the electron flow in each step.

   Benzyl chloride                    Nitromethane anion              Benzaldehyde     

Question: Reaction of (S)-3-methyl-2-pentanone with methyl magnesium bromide followed by acidification yields 2,3-dimethyl-2-pentanol. What is the stereochemistry of the product? Is the product optically active?

Testosterone is one of the most important male steroid hormones. When testosterone is dehydrated by treatment with acid, rearrangement occurs to yield the product shown. Propose a mechanism to account for this reaction.

p-Nitrophenol and 2,6-dimethyl-4-nitrophenol both have pKa 5 7.15, but 3,5-dimethyl-4-nitrophenol has pKa 5 8.25. Why is 3,5-dimethyl-4- nitrophenol so much less acidic?

2,3-Dimethyl-2,3-butanediol has the common name pinacol. On heating with aqueous acid, pinacol rearranges to pinacolone, 3,3-dimethyl-2-butanone. Suggest a mechanism for this reaction.

A problem often encountered in the oxidation of primary alcohols to acids is that esters are sometimes produced as by-products. For example, oxidation of ethanol yields acetic acid and ethyl acetate:

Propose a mechanism to account for the formation of ethyl acetate. Take into account the reversible reaction between aldehydes and alcohols:

Identify the reagents a–f in the following scheme:

As a rule, axial alcohols oxidize somewhat faster than equatorial alcohols. Which would you expect to oxidize faster, cis-4-tert-butylcyclohexanol or trans-4-tert-butylcyclohexanol? Draw the more stable chair conformation of each molecule.

Propose a synthesis of bicyclohexylidene, starting from cyclohexanone as the only source of carbon.

Dehydration of trans-2-methylcyclopentanol with POCl3 in pyridine yields predominantly 3-methylcyclopentene. Is the stereochemistry of this dehydration syn or anti? Can you suggest a reason for formation of the observed product? (Make molecular models!)

Galactose, a constituent of the disaccharide lactose found in dairy products, is metabolized by a pathway that includes the isomerization of UDP-galactose to UDP-glucose, where UDP = uridylyl diphosphate. The enzyme responsible for the transformation uses as cofactor. Propose a mechanism.

Compound A, ${\mathbf{C}}_8{\mathbf{H}}_{\mathbf{1}0}\mathbf{O}$ , has the IR and ${}^{\mathbf{1}}\mathbf{H}$ NMR spectra shown. Proposea structure consistent with the observed spectra, and label each peak inthe NMR spectrum. Note that the absorption at $\mathbf{5}\mathbf{.}\mathbf{5}\mathbf{\delta }$ disappears when ${\mathbf{D}}_{\mathbf{2}}\mathbf{O}$ is added.

The reduction of carbonyl compounds by reaction with hydride reagents $\left(H{:}^{-}\right)$ and the Grignard addition by reaction with organomagnesium halides $\left(R{:}^{-}{}^{+}\mathrm{MgBr}\right)$ are examples of nucleophilic carbonyl addition reactions. What analogous product do you think might result from reaction of cyanide ion with a ketone?

Ethers can be prepared by reaction of an alkoxide or phenoxide ion with a primary alkyl halide. Anisole, for instance, results from reaction of sodium phenoxide with iodomethane. What kind of reaction is occurring? Show the mechanism.

Give IUPAC names for the following compounds:

(a)

(b) 

(c)

(d)

Draw the structure of the carbonyl compound(s) from which each of the following alcohols might have been prepared, and show the products you would obtain by treatment of each alcohol with (1) Na metal, (2) ${\mathbf{SOCl}}_{\mathbf{2}}$, and (3) Dess-Martin periodinane.

(a)

(b)

Predict the product from reaction of the following substance (reddish brown=Br) with:

(a)${\mathbf{\text{PBr}}}_{\mathbf{3}}$

(b) Aqueous ${\mathbf{\text{H}}}_{\mathbf{2}}\mathit{S}{\mathit{O}}_{\mathbf{4}}$

(c) ${\mathbf{\text{SOCl}}}_{\mathbf{2}}$

(d)Dess-Martin periodinane

(e) ${\mathbf{\text{Br}}}_{\mathbf{2}}\mathbf{ }\mathbf{,}\mathbf{ }\mathit{F}\mathit{e}\mathit{B}{\mathit{r}}_{\mathbf{3}}$

Predict the product from reaction of the following substance with:

1. ${\mathbf{NaBH}}_4$ ; then ${\mathbf{H}}_3{\mathbf{O}}^{+}$ 
2. ${\mathbf{LiAlH}}_4$ ; then  ${\mathbf{H}}_3{\mathbf{O}}^{+}$ 

      3. $\mathbf{2}{\mathbf{CH}}_3{\mathbf{CH}}_2\mathbf{MgBr}$; then  ${\mathbf{H}}_3{\mathbf{O}}^{+}$

Name and assign R or S stereochemistry to the product (s) you would obtain by reaction of the following substance with ethylmagnesium bromide. Is the product chiral? Is it optically active? Explain.

Question: Evidence for the intermediate carbocations in the acid-catalyzed dehydration of alcohols comes from the observation that rearrangements sometimes occur. Propose a mechanism to account for the formation of 2,3-dimethyl-2-butene from 3,3-dimethyl-2-butanol.

Question:Acid-catalyzed dehydration of 2,2-dimethylcyclohexanol yields a mixture of 1,2-methylcyclohexane and isopropylidenecyclopentane. Propose a mechanism to account for the formation of both products.

Epoxides react with Grignard reagents to yield alcohols. Propose a mechanism.

Treatment of the following epoxide with aqueous acid produces a carbocation intermediate that reacts with water to give a diol product. Show the structure of the carbocation, and propose a mechanism for the second step.