Write the structure of the aldol condensation product of each of the aldehydes in 21.9

Write structural formulas for the two most stable enol isomers of the \(\beta\)-dicarbonyl compounds shown in a form that reflects an intramolecular hydrogen bond.

K for enolization of 2,4-cyclohexadienone is about 1013. Explain why the enol is so much more stable than the keto tautomer.

Chlorination of 2-butanone yields two isomeric products, each having the molecular formula C4H7ClO. (a) What are these two compounds? (b) Write structural formulas for the enol intermediates that lead to each of these compounds. (c) Using curved arrows, show the flow of electrons in the reaction of each of the enols with Cl2.

\(\alpha\)-Halogenation of 3-methylbutanoic acid has been used to prepare the amino acid valine. What is the structure of valine? When isolated from proteins, natural valine has a specific rotation \([\alpha]\) of +26°. What is the rotation of valine prepared via halogenation of 3-methylbutanoic acid? Text Transcription: alpha [alpha]

After the compound shown was heated in D2O containing K2CO3 at 70°C, the only signals that were observed in its 1H NMR spectrum were at \(\delta\) 3.9 ppm for the protons in the OCH3 group and at \(\delta\) 6.7–6.9 ppm for those on the aromatic ring. What happened? Text Transcription: delta

Use the structural formulas and pKa’s in Table 21.2 to estimate the equilibrium constant K for the reaction of ethoxide with (a) ethyl acetoacetate and (b) diethyl malonate. The pKa of ethanol is 16.

Write the structure of the aldol addition product of each of the following.

Each of the following can be prepared by an intramolecular aldol condensation of a diketone. Apply retrosynthetic analysis to deduce the structure of the diketone in each case.

Give the structure of the mixed aldol condensation product of benzaldehyde with

One of the following esters cannot undergo the Claisen condensation. Which one? Write structural formulas for the Claisen condensation products of the other two.

Write the structure of the Dieckmann cyclization product formed on treatment of each of the following diesters with sodium ethoxide, followed by acidification.

Give the structure of the product obtained when ethyl phenylacetate is treated with each of the following esters under conditions of the mixed Claisen condensation.

The pKa’s of ethyl acetoacetate and diethyl malonate are 11 and 13, respectively. Write a structural formula for the most stable enolate of each using resonance to show the electron delocalization in each enolate.

What is the product of each of the following reaction sequences?

Outline a synthesis of the compound shown.

Design a synthesis of cyclopentyl methyl ketone based on the partial retrosynthesis:

Which of the following is the most suitable for preparing a carboxylic acid by the haloform reaction? Give the structure of the carboxylic acid.

Mesityl oxide is an industrial chemical prepared by an aldol condensation. From what organic starting material is mesityl oxide prepared? It often contains about 10% of an isomer with the same carbon skeleton. What is the most likely structure for this contaminant?

Acrolein (H2C=CHCH=O) reacts with sodium azide (NaN3) in aqueous acetic acid to form a compound, C3H5N3O, in 71% yield. Propanal (CH3CH2CH=O), when subjected to the same reaction conditions, is recovered unchanged. Suggest a structure for the product formed from acrolein, and offer an explanation for the difference in reactivity between acrolein and propanal.

Outline a synthesis of the compound shown from methyl vinyl ketone and diethyl malonate.

Both conjugate addition and intramolecular aldol condensation can be carried out in one synthetic operation without isolating any of the intermediates. Write structural formulas corresponding to the intermediate formed in the conjugate addition step and in the aldol condensation step.

Outline two ways in which 4-methyl-2-octanone can be prepared by conjugate addition of an organocuprate to an \(\alpha, \beta\)-unsaturated ketone. Text Transcription: alpha, beta

Choose the compound in each of the following pairs that has the greater enol content.

Terreic acid, a naturally occurring antibiotic substance, is an enol isomer of the structure shown. Write the two most stable enols and choose the more stable one.

Consider the ketones piperitone, menthone, and isomenthone. Suggest reasonable explanations for each of the following observations. (a) (R)-(?)-Piperitone racemizes on standing in a solution of sodium ethoxide in ethanol. (b) Menthone is converted to a mixture of menthone and isomenthone on treatment with 90% sulfuric acid.

In each of the following, the indicated observations were made before any of the starting material was transformed to aldol addition or condensation products: (a) In aqueous acid, only 17% of (C6H5)2CHCH=O is present as the aldehyde; 2% of the enol is present. Some other species account for 81% of the material. What is it? (b) In aqueous base, 97% of (C6H5)2CHCH=O is present as a species different from any of those in part (a). What is this species?

(a ) In addition to one equivalent of methylmagnesium iodide to ethyl acetoacetate, the Grignard reagent is consumed, but the only organic product obtained after working up the reaction mixture is ethyl acetoacetate. Why? What happens to the Grignard reagent? (b) On repeating the reaction but using D2O and DCl to work up the reaction mixture, it is found that the recovered ethyl acetoacetate contains deuterium. Where is this deuterium located?

Give the structure of the expected organic product in the reaction of 3-phenylpropanal with each of the following: (a) Chlorine in acetic acid (b) Sodium hydroxide in ethanol, 10°C (c) Sodium hydroxide in ethanol, 70°C (d) Product of part (c) with lithium aluminum hydride; then H2O (e) Product of part (c) with sodium cyanide in acidic ethanol

Each of the following reactions has been reported in the chemical literature. Write the structure of the product(s) formed in each case.

Dibromination of camphor under the conditions shown gave a single product in 99% yield. What is this product?

Bromination of 3-methyl-2-butanone yielded two compounds, each having the molecular formula C5H9BrO in a 95:5 ratio. The 1H NMR spectrum of the major isomer A was characterized by a doublet at \(\delta\) 1.2 (six protons), a septet at \(\delta\) 3.0 (one proton), and a singlet at \(\delta\) 4.1 (two protons). The 1H NMR spectrum of the minor isomer B exhibited two singlets, one at \(\delta\) 1.9 and the other at \(\delta\) 2.5. The lower field singlet had half the area of the higher field one. Suggest reasonable structures for A and B. Text Transcription: delta

Treatment of 2-butanone (1 mol) with Br2 (2 mol) in aqueous HBr gave C4H6Br2O. The 1H NMR spectrum of the product was characterized by signals at \(\delta\) 1.9 (doublet, three protons), \(\delta\) 4.6 (singlet, two protons), and \(\delta\) 5.2 (quartet, one proton). Identify this compound. Text Transcription: delta

Give the structure of the principal organic product of each of the following reactions: (a) \(\text { Ethyl acetoacetate }+1 \text {-bromobutane } \stackrel{\mathrm{NaOCH}_{2} \mathrm{CH}_{3} \text {, ethanol }}{\longrightarrow}\) (c) \(\text { Acetophenone }+\text { diethyl carbonate } \frac{1 . \mathrm{NaOCH}_{2} \mathrm{CH}_{3}}{2 . \mathrm{H}_{3} \mathrm{O}^{+}}/) (d) \(\text { Acetone }+\text { diethyl oxalate } \frac{1 . \mathrm{NaOCH}_{2} \mathrm{CH}_{3}}{2 . \mathrm{H}_{3} \mathrm{O}^{+}}\) (e) \(\text { Diethyl malonate }+\text { 1-bromo-2-methylbutane } \stackrel{\mathrm{NaOCH}_{2} \mathrm{CH}_{3}, \text { ethanol }}{\longrightarrow}\) (g) \(\text { Diethyl malonate }+\text { 6-methyl-2-cyclohexenone } \stackrel{\mathrm{NaOCH}_{2} \mathrm{CH}_{3} \text {, ethanol }}{\longrightarrow}\) (h) \(\text { Product of part (g) } \stackrel{\mathrm{H}_{2} \mathrm{O}, \mathrm{HCl}, \text { heat }}{\longrightarrow}\) Text Transcription: Ethyl acetoacetate +1-bromobutane stackrel NaOCH_2CH_3, ethanol longrightarrow Acetophenone + diethyl carbonate 1. NaOCH_2CH_3/2. H_3O^+ Acetone + diethyl oxalate 1. NaOCH_2CH_3/2. H_3O^+ Diethyl malonate + 1-bromo-2-methylbutane stackrel NaOCH_2CH_3, ethanol longrightarrow Diethyl malonate + 6-methyl-2-cyclohexenone stackrel NaOCH_2CH_3, ethanol longrightarrow Product of part (g) stackrel H_2O, HCl, heat longrightarrow Text Transcription: delta

Give the structure of the product (C7H10O) formed by intramolecular aldol condensation of the keto-aldehyde shown.

The following questions pertain to the esters shown and behavior under conditions of the Claisen condensation. (a) Two of these esters are converted to \(\beta\)-keto esters in good yield on treatment with sodium ethoxide and subsequent acidification of the reaction mixture. Which two are these? Write the structure of the Claisen condensation product of each one. (b) One ester is capable of being converted to a \(\beta\)-keto ester on treatment with sodium ethoxide, but the amount of \(\beta\)-keto ester that can be isolated after acidification of the reaction mixture is quite small. Which ester is this? (c) One ester is incapable of reaction under conditions of the Claisen condensation. Which one? Why? Text Transcription: beta

(a) Give the structure of the Claisen condensation product of ethyl phenylacetate (C6H5CH2COOCH2CH3). (b) What ketone would you isolate after saponification and decarboxylation of this Claisen condensation product? (c) What ketone would you isolate after treatment of the Claisen condensation product of ethyl phenylacetate with sodium ethoxide and allyl bromide, followed by saponification and decarboxylation? (d) Give the structure of the mixed Claisen condensation product of ethyl phenylacetate and ethyl benzoate. (e) What ketone would you isolate after saponification and decarboxylation of the product in part (d)? (f ) What ketone would you isolate after treatment of the product in part (d) with sodium ethoxide and allyl bromide, followed by saponification and decarboxylation?

The following questions concern ethyl (2-oxocyclohexane)carboxylate. (a) Write a chemical equation showing how you could prepare ethyl (2-oxocyclohexane)-carboxylate by a Dieckmann cyclization. (b) Write a chemical equation showing how you could prepare ethyl (2-oxocyclohexane)-carboxylate by acylation of a ketone. (c) Write structural formulas for the two most stable enol forms of ethyl (2-oxocyclohexane)carboxylate. (d) Write the three most stable resonance contributors to the most stable enolate derived from ethyl (2-oxocyclohexane)carboxylate. (e) Show how you could use ethyl (2-oxocyclohexane)carboxylate to prepare 2-methylcyclohexanone. (f) Give the structure of the product formed on treatment of ethyl (2-oxocyclohexane)-carboxylate with acrolein (H2C=CHCH=O) in ethanol in the presence of sodium ethoxide.

Each of the reactions shown has been carried out in the course of some synthetic project and given the compound indicated by the molecular formula. What are those compounds?

The use of epoxides as alkylating agents for diethyl malonate provides a useful route to ?-lactones. Write equations illustrating such a sequence for styrene oxide as the starting epoxide. Is the lactone formed by this reaction 3-phenylbutanolide, or is it 4-phenylbutanolide?

The spicy flavor of cayenne pepper is due mainly to a substance called capsaicin. See if you can deduce the structure of capsaicin on the basis of its laboratory synthesis:

Jasmone, which contributes to the odor of jasmine, can be prepared by an intramolecular aldol condensation of a diketone. Use retrosynthetic analysis to deduce the structure of the diketone.

Prepare each of the following target molecules using the compounds shown as the sources of all of the carbons plus any necessary organic or inorganic reagents.

Compound A is difficult to prepare owing to its ready base-catalyzed isomerization to compound B. Write a reasonable mechanism for this isomerization.

The \(\alpha\)-methylene ketone sarkomycin has an inhibitory effect on certain types of tumors. A key step in the synthesis of sarkomycin is the reaction of lactone ester A with potassium tert-butoxide in tetrahydrofuran to give the bicyclic compound B. Write a mechanism for this reaction. Text Transcription: alpha

\(\beta\)-Lactones can be prepared in good yield from thioester enolates. Suggest a mechanism for the reaction shown. Text Transcription: beta

Outline a reasonable mechanism for each of the following reactions.

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. Predict the major organic product(s) of the following reaction. Text Transcription: alpha beta

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. What is the product of the reaction of the dianion in Problem 21.58 with cyclohexanone? Text Transcription: alpha beta

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. The regiochemistry of carbon–carbon bond formation between the dianion shown and styrene oxide is as indicated by the curved arrows: The product of this reaction is a hydroxy acid having the molecular formula C12H16O3, which cyclizes readily to give a lactone (C12H16O2). What is the structure of this lactone? Text Transcription: alpha beta

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. The dianion from ethyl acetoacetate was carried through the reaction sequence shown. What was the product (compound X)? Text Transcription: alpha beta

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. What pair of compounds is the most reasonable source of all of the carbon atoms if you wished to prepare the epoxy acid shown via a dianion? Text Transcription: alpha beta

The synthetic applications of carbanions as reagents for carbon–carbon bond formation have been highlighted numerous times throughout this text. All of the reagents covered so far have a net charge of –1; that is, they are monoanions. Are there others with a –2 charge (dianions), and, if so, how are they prepared, what are their properties, and how are they used in synthesis? Consider acetic acid: The pKa of acetic acid is 4.7, which corresponds to ionization of the O-H group. The pKa for ionization of a C-H bond of acetate ion is 33. None of the negative charge of the monoanion is shared by carbon. The dianion, however, has carbanionic character and the potential to act as a nucleophile in carbon–carbon bond-forming reactions. Diisopropylamine has a pKa of 36, which makes lithium diisopropylamide (LDA) a strong enough base to convert acetic acid to its dianion. Other carboxylic acids behave similarly to give dianions that undergo typical carbanion reactions. Alkylation of carboxylic acid dianions provide a useful alternative to the malonic ester synthesis. Experimentally, as in this example, it is sometimes useful to convert the carboxylic acid to its carboxylate (monoanion) with sodium hydride (NaH, step 1) before treating with LDA (step 2). Because the dianion is a strong base, the alkyl halide used in step 3 must be methyl or primary. A pH adjustment (step 4) converts the resulting carboxylate salt to the desired carboxylic acid. The dianions of \(\alpha\)-halocarboxylic acids give epoxy acids (called glycidic acids) on reaction with aldehydes and ketones. Dianions have been prepared from ?-keto esters by double deprotonation using a number of strong bases including LDA. Protons on the ? carbon of \(\beta\)-keto esters are flanked by two carbonyl groups and are far more acidic than those on the ? carbon. In the dianion, therefore, the ? carbon is more basic and more nucleophilic. Alkylation of the monoanion of \(\beta\)-keto acids occurs at the ? carbon. Alkylation of the dianion occurs at the ? carbon. \(\beta\)-Diketones behave similarly to \(\beta\)-keto esters. Sodium or potassium amide in liquid ammonia is a suitable base/solvent system in this case. Two dianions A and B are capable of being formed in the following reaction, but only a single alkylation product, isolated in 62% yield, was obtained. This product is not capable of cis–trans isomerism. Was this product formed from dianion A or dianion B? Text Transcription: alpha beta

Write structural formulas for the enol isomers of each of the following. (a) 2,2-Dimethyl-3-pentanone (b) Acetophenone (c) 2-Methylcyclohexanone (d) Methyl vinyl ketone

Find the most acidic hydrogen in each of the following and write a chemical equation for the proton-transfer process that occurs on reaction with hydroxide ion. Use curved arrows to show electron flow and label the acid, base, conjugate acid, and conjugate base. (a) tert-Butyl methyl ketone (b) 3-Methylbutanal (c) Methyl propanoate

Write the structure of the aldol condensation product of each of the aldehydes in Problem 21.9. One of these aldehydes can undergo aldol addition, but not aldol condensation. Which one? Why?

Chalcones are based on the parent structure shown above and are conveniently prepared by an aldol condensation. Use retrosynthetic analysis to identify the carbonyl compound and enolate and write an equation for the synthesis of chalcone.

Write an equation for the carbon–carbon bond-forming step in the cyclization just cited. Show clearly the structure of the enolate ion, and use curved arrows to represent its nucleophilic addition to the appropriate carbonyl group. Write a second equation showing dissociation of the tetrahedral intermediate formed in the carbon–carbon bond-forming step.

Use retrosynthetic analysis to choose the appropriate ?-dicarbonyl compound and alkyl halide to prepare each of the following: (a) 3-Methylpentanoic acid (b) 1-Phenyl-1,4-pentanedione (c) 4-Methylhexanoic acid (d) 5-Hexen-2-one

(a ) Only a small amount (less than 0.01%) of the enol form of diethyl malonate is present at equilibrium. Write a structural formula for this enol. (b) Enol forms are present to the extent of about 8% in ethyl acetoacetate. There are three constitutionally isomeric enols possible. Write structural formulas for these three enols. Which one do you think is the most stable? The least stable? Why? (c) Bromine reacts rapidly with both diethyl malonate and ethyl acetoacetate. The reaction is acid-catalyzed and liberates hydrogen bromide. What is the product formed in each reaction?

Give the structure of the product formed on reaction of ethyl acetoacetate with each of the following: (a) 1-Bromopentane and sodium ethoxide (b) Saponification (basic hydrolysis) and decarboxylation of the product in part (a) (c) Methyl iodide and the product in part (a) treated with sodium ethoxide (d) Saponification and decarboxylation of the product in part (c) (e) 1-Bromo-3-chloropropane and one equivalent of sodium ethoxide (f ) Product in part (e) treated with a second equivalent of sodium ethoxide (g) Saponification and decarboxylation of the product in part (f ) (h) Phenyl vinyl ketone and sodium ethoxide (i) Saponification and decarboxylation of the product in part (h)

Repeat the preceding problem for diethyl malonate.

Show how each of the following compounds could be prepared from 3-pentanone. In most cases more than one synthetic transformation will be necessary. (a) 2-Bromo-3-pentanone (b) 1-Penten-3-one (c) 1-Penten-3-ol (d) 3-Hexanone (e) 2-Methyl-1-phenyl-1-penten-3-one

Show how you could prepare each of the following compounds. Use the starting material indicated along with ethyl acetoacetate or diethyl malonate and any necessary inorganic reagents. Assume also that the customary organic solvents are freely available. (a) 4-Phenyl-2-butanone from benzyl alcohol (b) 3-Phenylpropanoic acid from benzyl alcohol (c) 2-Allyl-1,3-propanediol from propene (d) 4-Penten-1-ol from propene (e) 5-Hexen-2-ol from propene