Treatment of 1,1-diphenyl-1,2-epoxyethane with aqueous acid yields diphenylacetaldehyde as the major product. Propose a mechanism for the reaction.

Fluoxetine, a heavily prescribed antidepressant marketed under the

name Prozac, can be prepared by a route that begins with the reaction between a phenol and an alkyl chloride.

1. The rate of the reaction depends on both phenol and alkyl halide. Is this an SN1 or an SN2 reaction? Show the mechanism.
2. The physiologically active enantiomer of fluoxetine has (S) stereochemistry. Based on your answer in part (a), draw the structure of the alkyl chloride, you would need, showing the correct stereochemistry.

When 2-methyl-2,5-pentanediol is treated with sulfuric acid, dehydration occurs and 2,2 dimethyltetrahydrofuran is formed. Suggest a mechanism for this reaction. Which of the two oxygen atoms is most likely to be eliminated, and why?

Methyl aryl ethers, such as anisole, are cleaved to iodomethane and a phenoxide ion by treatment with LiI in hot DMF. Propose a mechanism for this reaction.

The herbicide acifluorfen can be prepared by a route that begins with reaction between a phenol and an aryl fluoride. Propose a mechanism.

Aldehydes and ketones undergo acid-catalyzed reaction with alcohols to yield hemiacetals, compounds that have one alcohol-like oxygen and one ether-like oxygen bonded to the same carbon. Further reaction of a hemiacetal with alcohol then yields an acetal, a compound that has two ether-like oxygens bonded to the same carbon.

(a) Show the structures of the hemiacetal and acetal you would obtain by reaction of cyclohexanone with ethanol.

(b) Propose a mechanism for the conversion of a hemiacetal into an acetal.

Propose a mechanism to account for the following transformation. What two kinds of reactions are occurring?

Draw structures corresponding to the following IUPAC names:

(a) Ethyl 1-ethylpropyl ether         (b) Di(p-chlorophenyl) ether

(c) 3,4-Dimethoxybenzoic acid    (d) Cyclopentyloxycyclohexane

(e) 4-Allyl-2-methoxyphenol (eugenol; from oil of cloves)

Give IUPAC names for the following structures:

How would you prepare the following ethers?

How would you prepare the following compounds from 1-phenylethanol?

(a) Methyl 1-phenylethyl ether       (b) Phenylepoxyethane

(c) tert-Butyl 1-phenylethyl ether    (d) 1-Phenylethanethiol

Question: tert-Butyl ethers can be prepared by the reaction of an alcohol with 2-methylpropene in the presence of an acid catalyst. Propose a mechanism for this reaction

Treatment of trans-2-chlorocyclohexanol with NaOH yields 1,2-epoxycyclohexane,but reaction of the cis isomer under the same conditions yields cyclohexanone. Propose mechanisms for both reactions, and explain why the different results are obtained.

Predict the products of the following ether cleavage reactions:

How would you carry out the following transformations? More than one step may be required.

(a) 

(b)  

(c)   

(d)    

(e)    

What product would you expect from cleavage of tetrahydrofuran

with HI?

Write the mechanism of the hydrolysis of cis-5,6-epoxydecane by reaction with aqueous acid. What is the stereochemistry of the product, assuming normal backside S_N2 attack?

What is the stereochemistry of the product from acid-catalyzed hydrolysis of trans-5,6-epoxydecane? How does the product differ from that formed in Problem 18-47?

Acid-catalyzed hydrolysis of a 1,2-epoxycyclohexane produces a transdiaxial 1,2-diol. What product would you expect to obtain from acidic hydrolysis of cis-3-tert-butyl-1,2-epoxycyclohexane? (Recall that the bulky tert-butyl group locks the cyclohexane ring into a specific conformation.)

Imagine that you have created (2R, 3R)-2,3-epoxy-3-methylpentane with aqueous acid to carry out a ring opening reaction.

1. Draw the epoxide showing stereochemistry.
2. Draw and name the product showing stereochemistry.
3. Is the product chiral? Explain.
4. Is the product optically active? Explain.

Epoxides are reduced by treatment with lithium aluminum hydride to yield alcohols. Propose a mechanism for this reaction.

Show the structure and stereochemistry of the alcohol that would result if 1,2-epoxycyclohexane were reduced with lithium aluminium deuteride, ${\mathbf{LiAlD}}_{\mathbf{4}}$?

The red fox (Vulpesvulpes) uses a chemical communication system based on scent marks in urine. One component of fox urine is a sulfide whose mass spectrum has ${\mathbf{M}}^{\mathbf{+}}\mathbf{=}\mathbf{116}$. IR spectroscopy shows an intense band at $\mathbf{890}{\mathbf{cm}}^{\mathbf{-}\mathbf{1}}$and ${}^{\mathbf{1}}\mathbf{H}$NMR spectroscopy reveals the following peaks:

Anethole, , ${\mathbf{C}}_{\mathbf{10}}{\mathbf{H}}_{\mathbf{12}}\mathbf{O}$a major constituent of the oil of anise, has the NMR spectrum shown. On oxidation with ${\mathbf{Na}}_{\mathbf{2}}{\mathbf{Cr}}_{\mathbf{2}}{\mathbf{O}}_{\mathbf{7}}$, anethole yields p-methoxybenzoic acid. What is the structure of anethole? Assign all peaks in the NMR spectrum, and account for the observed splitting patterns

Anethole, \({C_{10}}{H_{12}}O\), a major constituent of the oil of anise, has the \({}^1H\) NMR spectrum shown. On oxidation with \(N{a_2}C{r_2}{O_7}\), anethole yields p-methoxybenzoic acid. What is the structure of anethole? Assign all peaks in the NMR spectrum, and account for the observed splitting patterns.

Propose structures for compounds that have the following 1H NMR spectra:

 (a) C₅H₁₂S (An –SH proton absorbs near 1.6$\mathbf{\delta }$ )

                 (b)C₉H₁₁BRO

                        (c)C₅H₁₂O₂

Propose structures for compounds that have the following 1H NMR spectra:

(a) \({C_5}{H_{12}}S\) (An –SH proton absorbs near 1.6 \(\delta \) )

(b) \({C_9}{H_{11}}BrO\)

(c) \({C_5}{H_{12}}{O_2}\)

Predict the products of the following reactions:

(a) 

(b) 

(c)

(d)

Predict the products of the following reactions:

How would you synthesize anethole (Problem 18-54) from phenol?

 How could you prepare benzyl phenyl ether from benzene and phenol? More than one step is required.

Meerwein’s reagent, triethyloxoniumtetrafluoroborate, is a powerful ethylating agent that converts alcohols into ethyl ethers at neutral pH. Show the reaction of Meerwein’s reagent with cyclohexanol, and account for the fact that trialkyloxonium salts are much more reactive alkylating agents than alkyl iodides.

${\mathbf{\left(}{\mathbf{CH}}_{\mathbf{3}}{\mathbf{CH}}_{\mathbf{2}}\mathbf{\right)}}_{\mathbf{3}}{\mathit{O}}^{\mathbf{+}}\mathit{B}{{\mathbf{F}}_{\mathbf{4}}}^{\mathbf{-}}$ Meerwein’s reagent

Safrole, a substance isolated from the oil of sassafras, is used as a perfumery agent. Propose a synthesis of safrole from catechol (1,2-benzenediol).

Griginard reagents react with oxetane, a four membered cyclic ether, to yield primary alcohols, but the reaction is much slower than the corresponding reaction with ethylene oxide. Suggest a reason for the difference in reactivity between oxetane and ethylene oxide.

       Oxetane

How would you prepare o-Hydroxyphenylacetaldehyde from phenol? More than one step is required.

                            o-Hydroxyphenylacetaldehyde

Identify the reagents a-e in the following scheme:

Propose structures for compounds that have the following ¹H NMR spectra:

(a) ${\mathbf{\text{C}}}_{\mathbf{\text{4}}}{\mathbf{\text{H}}}_{\mathbf{\text{10}}}{\mathbf{\text{O}}}_{\mathbf{\text{2}}}$

(b) ${\mathbf{\text{C}}}_{\mathbf{\text{9}}}{\mathbf{\text{H}}}_{\mathbf{\text{10}}}\mathbf{\text{O}}$

We saw in section 17-4 that ketones react with ${\mathbf{\text{NaBH}}}_{\mathbf{\text{4}}}$ to yield alcohols. We’ll also see in section 22-3 that ketones react with ${\mathbf{\text{Br}}}_{\mathbf{\text{2}}}$ to yield $\mathit{\alpha }$-bromo ketones. Perhaps surprisingly, treatment with ${\mathbf{\text{NaBH}}}_{\mathbf{\text{4}}}$ of the $\mathit{\alpha }$ -bromo ketone from acetophenone yields an epoxide rather than a bromo alcohol. Show the structure of the epoxide, and explain its formation.

     Acetophenone                                An $\mathit{\alpha }$-bromo ketone

In nature, the enzyme chorismate mutase catalyses a Claisen rearrangement of chorismate that involves both the terminal double bond and the double bond with the highlighted carbon. What is the structure of prephenate, the biological precursor to the amino acids phenylalanine and tyrosine?

                        Chorismate

Predict the product(s) if the starting materials below underwent a Claisen rearrangement. Draw arrows to illustrate the rearrangement of electrons.

(a)

(b)

(c)