?The compound shown was required for the preparation of fluorescent markers for

Taking advantage of their large differences in pKa values, describe how a mixture of phenol and benzoic acid in diethyl ether solution could be separated. How could a mixture of phenol and cyclohexanol in diethyl ether solution be separated?

The compound shown was required for the preparation of fluorescent markers for biological compounds. How can it be synthesized from 2-chloro-3-hydroxy-4-methoxybenzaldehyde?

The aryl ethers shown are intermediates that have been used to make pharmaceutical drugs. Analyze their structures retro synthetically and suggest the appropriate phenol and alkyl halide from which each can be prepared.

Phenolic compounds such as BHT (butylated hydroxytoluene) are added to food products to retard spoilage. What is the structure of the radical that would be formed from BHT when it reacts with an alkyl radical R?? Write a resonance contributor for this radical.

The mechanism of the Claisen rearrangement of other allylic ethers of phenol is analogous to that of allyl phenyl ether. What is the product of the Claisen rearrangement of C6H5OCH2CH=CHCH3?

Name each of the following compounds:

Each of the following reactions has been reported in the chemical literature and proceeds in good yield. Identify the principal organic product in each case.

Reaction of phenol with 1,2-epoxypropane in aqueous sodium hydroxide at 150°C gives a single product, C9H12O2, at 90% yield. Suggest a reasonable structure for this compound.

In a study aimed at the synthesis of analogs of anthracycline antibiotics, 4,8-dimethoxynaphthalen-1-ol was converted to 4,8-dimethoxy-2-propanoylnaphthalen-1-ol by the following sequence of reactions. What is compound A?

A synthesis of the pain reliever phenacetin is outlined in the following equation. What is the structure of phenacetin?

Identify compounds A through C in the synthetic sequence represented by equations (a) through (c). (a) \(\text { Phenol }+\mathrm{H}_{2} \mathrm{SO}_{4} \stackrel{\text { heat }}{\longrightarrow} \text { Compound } \mathrm{A}\left(\mathrm{C}_{6} \mathrm{H}_{6} \mathrm{O}_{7} \mathrm{S}_{2}\right)\) (b) \(\text { Compound } \mathrm{A}+\mathrm{Br}_{2} \frac{1 . \mathrm{HO}^{-}}{2 . \mathrm{H}^{+}} \text {Compound } \mathrm{B}\left(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{BrO}_{7} \mathrm{S}_{2}\right)\) (c) \(\text { Compound } \mathrm{B}+\mathrm{H}_{2} \mathrm{O} \underset{\text { heat }}{\stackrel{\mathrm{H}^{+}}{\longrightarrow}} \text { Compound } \mathrm{C}\left(\mathrm{C}_{6} \mathrm{H}_{5} \mathrm{BrO}\right)\) Text Transcription: Phenol + H_2SO_4 stackrel heat longrightarrow Compound A (C_6H_6O_7 S_2) Compound A+Br_2 1. HO^-/2. H^+ Compound B (C_6H_5BrO_7S_2) Compound B+H_2O underset heat stackrel H^+longrightarrow Compound C (C_6H_5BrO)

Treatment of 3,5-dimethylphenol with dilute nitric acid, followed by steam distillation of the reaction mixture, gave a compound A (C8H9NO3, mp 66°C) in 36% yield. The nonvolatile residue from the steam distillation gave a compound B (C8H9NO3, mp 108°C) in 25% yield on extraction with chloroform. Identify compounds A and B.

As an allergen for testing purposes, synthetic 3-pentadecylcatechol is more useful than natural poison ivy extracts (of which it is one component). A stable crystalline solid, it is efficiently prepared in pure form from readily available starting materials. Outline a reasonable synthesis of this compound from 2,3-dimethoxybenzaldehyde and any necessary organic or inorganic reagents.

The following retrosynthetic analysis summarizes a synthetic plan that has been executed in four separate steps. Write equations appropriate for those steps.

Tamoxifen is an estrogen receptor modulator that is used in the treatment of breast cancer. Provide the missing reagents and the structure of compound A in the synthesis of tamoxifen.

Devise a synthesis of the compound shown on the left from the indicated starting materials and any other necessary reagents.

Pentafluorophenol is readily prepared by heating hexafluorobenzene with potassium hydroxide in tert-butyl alcohol: What is the most reasonable mechanism for this reaction? Comment on the comparative ease with which this conversion occurs.

In a general reaction known as the cyclohexadienone–phenol rearrangement, cyclohexadienones are converted to phenols under conditions of acid catalysis. An example is Write a reasonable mechanism for this reaction.

Treatment of p-hydroxybenzoic acid with aqueous bromine leads to the evolution of carbon dioxide and the formation of 2,4,6-tribromophenol. Explain.

One of the industrial processes for the preparation of phenol, discussed in Section 23.6, includes an acid-catalyzed rearrangement of cumene hydroperoxide as a key step. This reaction proceeds by way of an intermediate hemiketal: You learned in Section 18.8 of the relationship among hemiketals, ketones, and alcohols; the formation of phenol and acetone is an example of hemiketal hydrolysis. The formation of the hemiketal intermediate is a key step in the synthetic procedure; it is the step in which the aryl–oxygen bond is generated. Can you suggest a reasonable mechanism for this step?

One of the industrial processes for the preparation of phenol, discussed in Section 23.6, includes an acid-catalyzed rearrangement of cumene hydroperoxide as a key step. This reaction proceeds by way of an intermediate hemiketal: You learned in Section 18.8 of the relationship among hemiketals, ketones, and alcohols; the formation of phenol and acetone is an example of hemiketal hydrolysis. The formation of the hemiketal intermediate is a key step in the synthetic procedure; it is the step in which the aryl–oxygen bond is generated. Can you suggest a reasonable mechanism for this step?

Compound A undergoes hydrolysis of its acetal function in dilute sulfuric acid to yield 1,2-ethanediol and compound B (C6H6O2), mp 54°C. Compound B exhibits a carbonyl stretching band in the infrared at 1690 cm?1 and has two singlets in its 1H NMR spectrum, at \(\beta\) 2.9 and 6.7, in the ratio 2:1. On standing in water or ethanol, compound B is converted cleanly to an isomeric substance, compound C, mp 172–173°C. Compound C has no peaks attributable to carbonyl groups in its infrared spectrum. Identify compounds B and C. Text Transcription: beta

Identify the following compounds on the basis of the information provided: (a) C9H12O: Its IR and 13C NMR spectra are shown in Figure 23.3. (b) C9H11BrO: Its IR and 13C NMR spectra are shown in Figure 23.4.

Aryllithium reagents are familiar to us as the products of the reaction of aryl halides with lithium. A second route to aryllithiums is by deprotonation of an aromatic ring with an alkyllithium reagent. This process is called metalation. Although reasonable from an acid–base perspective (stronger acid on the left, weaker acid on the right), reactions such as this are inconveniently slow and not practical as a general method for making aryllithiums. Certain substitutents on an aromatic ring, however, both promote metalation and control its regioselectivity. These directed metalations are regioselective for lithiation at carbons ortho to the substituent. The substituents contain atoms, especially oxygen and nitrogen, capable of coordinating to lithium. This coordination is reflected in the transition state for proton abstraction and causes lithiation to be fastest at the carbons ortho to the substituent. Typical conditions for metalation involve treating a diethyl ether or tetrahydrofuran solution of the aryl derivative with an alkyllithium in hexane. N,N,N?,N?-Tetramethylethylenediamine [(CH3)2NCH2CH2N(CH3)2, TMEDA] is sometimes added to increase the rate of metalation. Once formed, the ortho-metalated derivative undergoes the usual reactions of organolithium reagents. The directing effects associated with electrophilic aromatic substitution play no role in directed metalation. Likewise, steric effects are not very important. It is common, for example, for metalation to occur at C-2 of a 1,3-disubstituted benzene. 4-Methoxybenzoic acid was metalated and allowed to react with methyl iodide as shown in the equation. (Two molar equivalents of sec-butyllithium are required because one equivalent is needed to deprotonate the CO2H group.) Predict the major product of the analogous methylation of 2-methoxybenzoic acid.

Aryllithium reagents are familiar to us as the products of the reaction of aryl halides with lithium. A second route to aryllithiums is by deprotonation of an aromatic ring with an alkyllithium reagent. This process is called metalation. Although reasonable from an acid–base perspective (stronger acid on the left, weaker acid on the right), reactions such as this are inconveniently slow and not practical as a general method for making aryllithiums. Certain substitutents on an aromatic ring, however, both promote metalation and control its regioselectivity. These directed metalations are regioselective for lithiation at carbons ortho to the substituent. The substituents contain atoms, especially oxygen and nitrogen, capable of coordinating to lithium. This coordination is reflected in the transition state for proton abstraction and causes lithiation to be fastest at the carbons ortho to the substituent. Typical conditions for metalation involve treating a diethyl ether or tetrahydrofuran solution of the aryl derivative with an alkyllithium in hexane. N,N,N?,N?-Tetramethylethylenediamine [(CH3)2NCH2CH2N(CH3)2, TMEDA] is sometimes added to increase the rate of metalation. Once formed, the ortho-metalated derivative undergoes the usual reactions of organolithium reagents. The directing effects associated with electrophilic aromatic substitution play no role in directed metalation. Likewise, steric effects are not very important. It is common, for example, for metalation to occur at C-2 of a 1,3-disubstituted benzene. Even though the following sequence, reported in the chemical literature, includes an unfamiliar reaction, you should be able to deduce the structure of the product from among the possible choices.

Aryllithium reagents are familiar to us as the products of the reaction of aryl halides with lithium. A second route to aryllithiums is by deprotonation of an aromatic ring with an alkyllithium reagent. This process is called metalation. Although reasonable from an acid–base perspective (stronger acid on the left, weaker acid on the right), reactions such as this are inconveniently slow and not practical as a general method for making aryllithiums. Certain substitutents on an aromatic ring, however, both promote metalation and control its regioselectivity. These directed metalations are regioselective for lithiation at carbons ortho to the substituent. The substituents contain atoms, especially oxygen and nitrogen, capable of coordinating to lithium. This coordination is reflected in the transition state for proton abstraction and causes lithiation to be fastest at the carbons ortho to the substituent. Typical conditions for metalation involve treating a diethyl ether or tetrahydrofuran solution of the aryl derivative with an alkyllithium in hexane. N,N,N?,N?-Tetramethylethylenediamine [(CH3)2NCH2CH2N(CH3)2, TMEDA] is sometimes added to increase the rate of metalation. Once formed, the ortho-metalated derivative undergoes the usual reactions of organolithium reagents. The directing effects associated with electrophilic aromatic substitution play no role in directed metalation. Likewise, steric effects are not very important. It is common, for example, for metalation to occur at C-2 of a 1,3-disubstituted benzene. The methoxymethyl group is an acetal, easily removed by acid hydrolysis. What are the products of the following hydrolysis?.

Aryllithium reagents are familiar to us as the products of the reaction of aryl halides with lithium. A second route to aryllithiums is by deprotonation of an aromatic ring with an alkyllithium reagent. This process is called metalation. Although reasonable from an acid–base perspective (stronger acid on the left, weaker acid on the right), reactions such as this are inconveniently slow and not practical as a general method for making aryllithiums. Certain substitutents on an aromatic ring, however, both promote metalation and control its regioselectivity. These directed metalations are regioselective for lithiation at carbons ortho to the substituent. The substituents contain atoms, especially oxygen and nitrogen, capable of coordinating to lithium. This coordination is reflected in the transition state for proton abstraction and causes lithiation to be fastest at the carbons ortho to the substituent. Typical conditions for metalation involve treating a diethyl ether or tetrahydrofuran solution of the aryl derivative with an alkyllithium in hexane. N,N,N?,N?-Tetramethylethylenediamine [(CH3)2NCH2CH2N(CH3)2, TMEDA] is sometimes added to increase the rate of metalation. Once formed, the ortho-metalated derivative undergoes the usual reactions of organolithium reagents. The directing effects associated with electrophilic aromatic substitution play no role in directed metalation. Likewise, steric effects are not very important. It is common, for example, for metalation to occur at C-2 of a 1,3-disubstituted benzene. A synthesis of a natural product (broussonin A) began with metalation and trimethylsilylation of compound 1 to give 2. Compound 2 was metalated and the resulting organolithium reagent treated with 3-(p-benzyloxy)propanal to give compound 3. Subsequent transformations of 3 gave broussonin A (C16H18O3). Which of the choices is most reasonable for compound 3?

Write structural formulas for each of the following compounds: (a) Pyrogallol (1,2,3-benzenetriol) (b) o-Benzylphenol (c) 3-Nitro-1-naphthol

One of the hydroxybenzoic acids is known by the common name salicylic acid. Its methyl ester, methyl salicylate, occurs in oil of wintergreen. Methyl salicylate boils over 50°C lower than either of the other two methyl hydroxybenzoates. What is the structure of methyl salicylate? Why is its boiling point so much lower than that of either of its regioisomers?

Which is the stronger acid in each of the following pairs? Explain your reasoning. (a) Phenol or p-hydroxybenzaldehyde (b) m-Cyanophenol or p-cyanophenol (c) o-Fluorophenol or p-fluorophenol

Aryl esters undergo a reaction called the Fries rearrangement in the presence of aluminum chloride. What two products are formed in the Fries rearrangement of phenyl benzoate?

Each of the following reactions has been reported in the chemical literature and gives a single organic product in high yield. Identify the product in each case. (a) 3-Benzyl-2,6-dimethylphenol treated with bromine in chloroform (b) 4-Bromo-2-methylphenol treated with 2-methylpropene and sulfuric acid (c) 2-Isopropyl-5-methylphenol (thymol) treated with sodium nitrite and dilute hydrochloric acid (d) 4-Methylphenol treated with propanoyl chloride and aluminum chloride

Write chemical equations expressing each of the following: (a) Preparation of o-nitrophenyl acetate by sulfuric acid catalysis of the reaction between a phenol and an acid anhydride. (b) Esterification of 2-naphthol with acetic anhydride in aqueous sodium hydroxide (c) Reaction of phenol with benzoyl chloride

The IUPAC rules permit the use of common names for a number of familiar phenols and aryl ethers. These common names are listed here along with their systematic names. Write the structure of each compound. (a) Vanillin (4-hydroxy-3-methoxybenzaldehyde): a component of vanilla bean oil, which contributes to its characteristic flavor (b) Thymol (2-isopropyl-5-methylphenol): obtained from oil of thyme (c) Carvacrol (5-isopropyl-2-methylphenol): present in oil of thyme and marjoram (d) Eugenol (4-allyl-2-methoxyphenol): obtained from oil of cloves (e) Gallic acid (3,4,5-trihydroxybenzoic acid): prepared by hydrolysis of tannins derived from plants (f) Salicyl alcohol (o-hydroxybenzyl alcohol): obtained from bark of poplar and willow trees

Write a balanced chemical equation for each of the following reactions: (a) Phenol + sodium hydroxide (b) Product of part (a) + ethyl bromide (c) Product of part (a) + butyl p-toluenesulfonate (d) Product of part (a) + acetic anhydride (e) o-Cresol + benzoyl chloride (f ) m-Cresol + ethylene oxide (g) 2,6-Dichlorophenol + bromine (h) p-Cresol + excess aqueous bromine (i) Isopropyl phenyl ether + excess hydrogen bromide + heat

Which phenol in each of the following pairs is more acidic? Justify your choice. (a) 2,4,6-Trimethylphenol or 2,4,6-trinitrophenol (b) 2,6-Dichlorophenol or 3,5-dichlorophenol (c) 3-Nitrophenol or 4-nitrophenol (d) Phenol or 4-cyanophenol (e) 2,5-Dinitrophenol or 2,6-dinitrophenol

Outline a reasonable synthesis of 4-nitrophenyl phenyl ether from chlorobenzene and phenol.

Choose the reaction in each of the following pairs that proceeds at the faster rate. Explain your reasoning. (a) Basic hydrolysis of phenyl acetate or m-nitrophenyl acetate (b) Basic hydrolysis of m-nitrophenyl acetate or p-nitrophenyl acetate (c) Reaction of ethyl bromide with phenol or with the sodium salt of phenol (d) Reaction of ethylene oxide with the sodium salt of phenol or with the sodium salt of p-nitrophenol (e) Bromination of phenol or phenyl acetate

Treatment of phenol with excess aqueous bromine is actually more complicated than expected. A white precipitate forms rapidly, which on closer examination is not 2,4,6-tribromophenol but is instead 2,4,4,6-tetrabromocyclohexadienone. Explain the formation of this product.