Aldehydes and Ketones: Nucleophilic Addition Reactions

Draw structures corresponding to the following names:

(a) 3-Methylbutanal (b) 4-Chloro-2-pentanone

(c) Phenylacetaldehyde (d) cis-3-tert-Butylcyclohexanecarbaldehyde

(e) 3-Methyl-3-butenal (f) 2-(1-Chloroethyl)-5-methylheptanal

Name the following aldehydes and ketones:

How would you prepare pentanal from the following starting materials?

(a) CH₃CH₂CH₂CH₂CH₂OH (b) CH₃CH₂CH₂CH₂CH=CH₂

(c) CH₃CH₂CH₂CH₂CO₂CH₃ (d) CH₃CH₂CH₂CH=CH₂

How would you carry out the following reactions? More than one step may be

required.

(a) 3-Hexyne  3-Hexanone

(b) Benzenem-Bromoacetophenone

(c) Bromobenzene Acetophenone

(d) 1-Methylcyclohexene  2-Methylcyclohexanone

p-Nitrobenzaldehyde is more reactive toward nucleophilic additions than p-methoxybenzaldehyde. Explain.

Treatment of an aldehyde or ketone with cyanide ion (${}^{-}\mathbf{:}\mathbf{C}\equiv \mathbf{N}$), followed by protonation of the tetrahedral alkoxide ion intermediate, gives a cyanohydrin.

Show the structure of the cyanohydrin obtained from cyclohexanone.

When dissolved in water, trichloroacetaldehyde exists primarily as its hydrate, called chloral hydrate. Show the structure of chloral hydrate.

The oxygen in water is primarily (99.8%) 16O, but water enriched with the heavy isotope ${}^{18}\mathbf{O}$ is also available. When an aldehyde or ketone is dissolved in ${}^{18}\mathbf{O}$-enriched water, the isotopic label becomes incorporated into the carbonyl group. Explain.

${\mathbf{R}}_2\mathbf{C}\mathbf{=}\mathbf{O}\mathbf{+}{\mathbf{H}}_2\mathbf{O}\rightleftharpoons {\mathbf{R}}_2\mathbf{C}\mathbf{=}\mathbf{O}\mathbf{+}{\mathbf{H}}_2\mathbf{O}$ where O = ${}^{18}\mathbf{O}$

Cyclohexanone forms a cyanohydrin in good yield but 2,2,6-trimethylcyclohexanonedoes not. Explain.

Imine formation is reversible. Show all the steps involved in the acid-catalyzed reaction of an imine with water (hydrolysis) to yield an aldehyde or ketone plus primary amine.

Draw the following molecule as a skeletal structure, and show how it can be prepared from a ketone and an amine.

Show the products you would obtain by acid-catalyzed reaction of cyclohexanonewith ethylamine, CH₃CH₂NH₂, and with diethylamine, (CH₃CH₂)₂NH.

How might conjugate addition reactions of lithium diorganocopper reagents be used to synthesize the following compounds?

Show all the steps in the acid-catalyzed formation of a cyclic acetal from ethylene glycol and an aldehyde or ketone.

Identify the carbonyl compound and the alcohol that were used to prepare the following acetal:

What carbonyl compound and what phosphorus ylide might you use to prepare each of the following compounds?

(a)

(b)

(c)

(d)

(e)

(f)

When o-phthalaldehyde is treated with base, o-(hydroxymethyl)benzoic acid is formed. Show the mechanism of this reaction.

What is the stereochemistry of the pyruvate reduction shown in Figure 19-12? Does NADH lose its pro-R or pro-S hydrogen? Does addition occur to the Si face or Re face of pyruvate? (Review Section 5-11.)

Treatment of 2-cyclohexenone with HCN/KCN yields a saturated keto nitrile rather than an unsaturated cyanohydrin. Show the structure of the product,

and propose a mechanism for the reaction.

How might you use IR spectroscopy to determine whether reaction between2-cyclohexenoneand lithium dimethylcopper gives the direct addition productor the conjugate addition product?

How might you use mass spectrometry to distinguish between the following pairs of isomers?

(a) 3-Methyl-2-hexanone and 4-methyl-2-hexanone

(b) 3-Heptanone and 4-heptanone

(c) 2-Methylpentanal and 3-methylpentanal

Describe the prominent IR absorptions and mass spectral peaks you would expect for the following compound:

Question: Predict the products of the wolff-Kishner reduction reactions below. Provide the electron pushing mechanism for each, beginning from the hydrazone intermediate.

Each of the following substances can be prepared by a nucleophilic

addition reaction between an aldehyde or ketone and a nucleophile.

Identify the reactants from which each was prepared. If the substance is an acetal, identify the carbonyl compound and the alcohol; if it is animine, identify the carbonyl compound and the amine; and so forth.

The following molecular model represents a tetrahedral intermediate resulting from addition of a nucleophile to an aldehyde or ketone. Identify the reactants, and write the structure of the final product when the nucleophilic addition reaction is complete.

The enamine prepared from acetone and dimethylamine is shown in its

lowest-energy form.

(a) What is the geometry and hybridization of the nitrogen atom?

(b) What orbital on nitrogen holds the lone pair of electrons?

(c) What is the geometric relationship between the p orbitals of the

double bond and the nitrogen orbital that holds the lone pair? Why

do you think this geometry represents the minimum energy?

Predict the product(s) and provide the mechanism for each reaction below. What does each mechanism have in common?

Predict the product(s) and provide the mechanism for each reaction below. What does each mechanism have in common?

Predict the product(s) and provide the mechanism for each reaction below. What does each mechanism have in common?

Question: Predict the product(s) and provide the mechanism for each reaction below. What does each mechanism have in common?

It is not uncommon for organic chemists to prepare acetals by an exchange-type process known as transacetalization. Predict the product(s) and show the mechanism for the transacetalization reactions below.

a. 

b. 

One of the steps in metabolism of fats is the reaction of an unsaturated acyl coA with water to give a $\beta$ - hydroxyacyl CoA. Propose a mechanism.

Ketones react with dimethylsulfonium methylide to yield epoxides. Suggest a mechanism for the reaction.

When cyclohexanone is heated in the presence of a large amount of acetone cyanohydrin and a small amount of base, cyclohexanone cyanohydrin and acetone are formed. Propose a mechanism.

Paraldehyde, a sedative, and hypnotic agent, is prepared by treatment of acetaldehyde with an acidic catalyst. Propose a mechanism for the reaction.

The Meerwein–Ponndorf–Verley reaction involves the reduction of a ketone by treatment with an excess of aluminum triisopropoxide,${\left[{\left({\mathbf{CH}}_3\right)}_2\mathbf{CHO}\right]}_3\mathbf{Al}$ . The mechanism of the process is closely related to the Cannizzaro reaction in that a hydride ion acts as a leaving group. Propose a mechanism.

Propose a mechanism to account for the formation of 3,5-dimethyl pyrazole from hydrazine and 2,4-pentanedione. Look carefully to see what has happened to each carbonyl carbon in going from starting material to product.

In light of your answer to Problem 19-46, propose a mechanism for the formation of 3, 5-dimethylisoxazole from hydroxylamine and 2,4-pentanedione

Trans alkenes are converted into their cis isomers and vice versa on epoxidation followed by treatment of the epoxide with triphenylphosphine. Propose a mechanism for the $\mathbf{epoxide}\to \mathbf{alkene}$ reaction.

Treatment of an $\alpha , \beta$ -unsaturated ketone with basic aqueous hydrogen peroxide yields an epoxy ketone. The reaction is specific to unsaturated ketones; isolated alkene double bonds do not react. Propose a mechanism.

Primary amines react with esters to yield amides: RCO₂R^' + R^"NH₂ $\to$RCONHR^" + R^'OH  . Propose a mechanism for the following reaction of an a b-unsaturated ester.

When crystals of pure $\alpha$ -glucose are dissolved in water, isomerization occurs slowly to produce  $\beta$-glucose. Propose a mechanism for isomerization.

The Wharton reaction converts an epoxy ketone to an allylic alcohol by reaction with hydrazine. Propose a mechanism. (Hint: Review the Wolff–Kishner reaction in Section 19-9.)

Draw structures corresponding to the following names:

1. Bromoacetone
2. (S)-2-Hydroxypropanal
3. 2-Methyl-3-heptanone
4. (2S,3R)-2,3,4-Trihydroxybutanal
5. 2,2,4,4-Tetramethyl-3-pentanone
6. 4-Methyl-3-penten-2-one
7. Butanedial
8. 3-Phenyl-2-propenal
9. 6,6-Dimethyl-2,4-cyclohexadienone
10. p-Nitroacetophenone

Draw and name the seven aldehydes and ketones with the formula ${\mathbf{C}}_5{\mathbf{H}}_{10}\mathbf{O}$ . Which are chiral?

Give IUPAC names for the following compounds:

(a)

(b)

(c)

(d)

(e) 

(f) 

Draw structures of compounds that fit the following descriptions:

1. An  $\mathit{\alpha }$,$\mathbf{\beta }$-unsaturated ketone, ${\mathbf{C}}_6{\mathbf{H}}_8\mathbf{O}$ 
2. An $\mathit{\alpha }$-diketone
3. An aromatic ketone,${\mathbf{C}}_9{\mathbf{H}}_{10}\mathbf{O}$ 
4. A diene aldehyde,${\mathbf{C}}_7{\mathbf{H}}_8\mathbf{O}$

How would you use a Grignard reaction on an aldehyde or ketone to synthesize the following compounds?

1. 2-Pentanol
2. 1-Butanol
3. 1-Phenylcyclohexanol
4. Diphenylmethanol

How might you carry out the following selective transformations? One of the two schemes requires a protection step. (Recall from Section 19-4 that aldehydes are more reactive than ketones towards nucleophilic addition.)

      b. 

Carvone is the major constituent of spearmint oil. What products would you expect from reaction of carvone with the following reagents?

1. ${\left({\mathbf{CH}}_3\right)}_2{\mathbf{Cu}}^{-}{\mathbf{Li}}^{+}$, then ${\mathbf{H}}_3{\mathbf{O}}^{+}$ 
2. ${\mathbf{LiAlH}}_4$, then ${\mathbf{H}}_3{\mathbf{O}}^{+}$
3.  ${\mathbf{CH}}_3{\mathbf{NH}}_2$
4. ${\mathbf{C}}_6{\mathbf{H}}_5\mathbf{MgBr}$, then ${\mathbf{H}}_3{\mathbf{O}}^{+}$
5. ${\mathbf{H}}_2\mathbf{/}\mathbf{Pd}$
   
6. ${\mathbf{CrO}}_3$, ${\mathbf{H}}_3{\mathbf{O}}^{+}$
7. ${\left({\mathbf{C}}_6{\mathbf{H}}_5\right)}_3{\mathbf{P}}^{+}{}^{-}\mathbf{CHCH}_3$
   
8. ${\mathbf{HOCH}}_2{\mathbf{CH}}_2\mathbf{OH}$, HCl