Solved: Although 2-substituted 2-cyclopentenones are in a base-catalyzed equilibrium

Show the steps in preparing each of the following substances using either a malonic ester synthesis or an acetoacetic ester synthesis:

Unlike most b-diketones, the following b-diketone has no detectable enol content and is about as acidic as acetone. Explain.

For a given a hydrogen atom to be acidic, the C]H bond must be parallel to the p orbitals of the C5O double bond (that is, perpendicular to the plane of the adjacent carbonyl group). Identify the most acidic hydrogen atom in the conformation shown for the following structure. Is it axial or equatorial?

Identify all the acidic hydrogens (pKa , 25) in the following molecules: (a) (b) O O COCl (e) (c) (d) O O (f) O CH3CH2CHCCH3 CH3 HOCH2CH2CC CCH3 CH3 CH3CH2CC CH2

Rank the following compounds in order of increasing acidity: CH3CCH2CCH3 CH (e) 3COCH3 (d) CCl (f) 3CO2H (a) CH3CH2CO2H (b) CH3CH2OH (CH3CH2) (c) 2NH

Write resonance structures for the following anions: (a) (b) O (d) (e) (c) CH3CCHCCH3 O O CH3CH CHCHCCH3 O N CCHCOCH3

Base treatment of the following a,b-unsaturated carbonyl compound yields an anion by removal of H1 from the g carbon. Why are hydrogens on the g carbon atom acidic? LDA C O C C C H H H C H O C C  H H H C   H

Treatment of 1-phenyl-2-propenone with a strong base such as LDA does not yield an anion, even though it contains a hydrogen on the carbon atom next to the carbonyl group. Explain. C 1-Phenyl-2-propenone

Predict the product(s) of the following reactions: (a) CO2H (b) O O CO2H CH3CH2CH2COH ? (c) O Br2, PBr3 ? Heat ? (d) NaOH, H2O I2 ? H2O ?

Which, if any, of the following compounds can be prepared by a malonic ester synthesis? Show the alkyl halide you would use in each case. (a) Ethyl pentanoate (b) Ethyl 3-methylbutanoate (c) Ethyl 2-methylbutanoate (d) Ethyl 2,2-dimethylpropanoate

Which, if any, of the following compounds can be prepared by an acetoacetic ester synthesis? Explain. (a) (b) (c) C CH2CCH3

How would you prepare the following ketones using an acetoacetic ester synthesis? CH3CH2CHCCH3 O O CH3CH2CH2CHCCH3 CH2CH3 CH3

How would you prepare the following compounds using either an acetoacetic ester synthesis or a malonic ester synthesis? CH3CCO2Et CO2Et CH3 H2C CHCH2CH2CCH3

(a) CH3COCH3 (b) Acetophenone (c) CH3CH2CHO (d) CH3CO2H (e) CH3CN

How might you convert geraniol into either ethyl geranylacetate or geranylacetone? CO2Et Ethyl geranylacetate CH2OH Geraniol Geranylacetone ? O

Aprobarbital, a barbiturate once used in treating insomnia, is synthesized in three steps from diethyl malonate. Show how you would synthesize the necessary dialkylated intermediate, and then propose a mechanism for the reaction of that intermediate with urea to give aprobarbital. H2N NH2 C O Aprobarbital

One way to determine the number of acidic hydrogens in a molecule is to treat the compound with NaOD in D2O, isolate the product, and determine its molecular weight by mass spectrometry. For example, if cyclohexanone is treated with NaOD in D2O, the product has MW 5 102. Explain how this method works.

When optically active (R)-2-methylcyclohexanone is treated with either aqueous base or acid, racemization occurs. Explain.

Would you expect optically active (S)-3-methylcyclohexanone to be racemized on acid or base treatment in the same way as 2-methylcyclohexanone (Problem 22.34)? Explain.

When an optically active carboxylic acid such as (R)-2-phenylpropanoic acid is brominated under HellVolhardZelinskii conditions, is the product optically active or racemic? Explain.

Fill in the reagents ac that are missing from the following scheme: a CH3 b c CO2CH3 O O CO2CH3 O CH3 O H3C CH3

Nonconjugated b,g-unsaturated ketones, such as 3-cyclohexenone, are in an acid-catalyzed equilibrium with their conjugated a,b-unsaturated isomers. Propose a mechanism for this isomerization.  H3O+

The interconversion of unsaturated ketones described in Problem 22.38 is also catalyzed by base. Explain.

One consequence of the base-catalyzed isomerization of unsaturated ketones described in Problem 22.39 is that 2-substituted 2-cyclopentenones can be interconverted with 5-substituted 2-cyclopentenones. Propose a mechanism for this isomerization. O OH O CH3 CH3

Although 2-substituted 2-cyclopentenones are in a base-catalyzed equilibrium with their 5-substituted 2-cyclopentenone isomers (Problem 22.40), the analogous isomerization is not observed for 2-substituted 2-cyclohexenones. Explain. OH O C

Using curved arrows, propose a mechanism for the following reaction, one of the steps in the metabolism of the amino acid alanine. 2O3POCH2 +N H CH3 OH N C H3C H CO2 Base 2O3POCH2 N H CH3 OH N C CH3 CO2

Using curved arrows, propose a mechanism for the following reaction, one of the steps in the biosynthesis of the amino acid tyrosine. CO2 O O HO O O CO2 C O + CO2

All attempts to isolate primary and secondary nitroso compounds result only in the formation of oximes. Tertiary nitroso compounds, however, are stable. Explain. A 3 nitroso compound (stable)

How would you synthesize the following compounds from cyclohexanone? More than one step may be required. (a) (b) CH (c) CH 2Br 2 CH2C6H5 O (d) (e) CO (f) CH2CH2CO2H 2H O

The two isomers cis- and trans-4-tert-butyl-2-methylcyclohexanone are interconverted by base treatment. Which isomer do you think is more stable, and why?

The following synthetic routes are incorrect. What is wrong with each? (a) O CH3CH2CH2CH2COEt CH3CH2CH CHCOEt O 1. Br2, CH3CO2H 2. Pyridine, heat (c) O CH3CCH2COEt H2C CHCH2CH2COH O O CHCH2Br 1. Na+ OEt 2. H2C 3. H3O+, heat (b) CO2Et CH3CHCO2Et CH3 CHCO2H 1. Na+ OEt 2. PhBr 3. H3O+, heat

Attempted Grignard reaction of cyclohexanone with tert-butylmagnesium bromide gives only about 1% yield of the expected addition product along with 99% unreacted cyclohexanone. If D3O1 is added to the reaction mixture after a suitable period, however, the unreacted cyclohexanone is found to have one deuterium atom incorporated into it. Explain. + 1% 99% 1. (CH3)3CMgBr 2. D3O+ O C(CH3)3

One of the later steps in glucose biosynthesis is the isomerization of fructose 6-phosphate to glucose 6-phosphate. Propose a mechanism, using acid or base catalysis as needed. Fructose 6-phosphate CH2OH C O O HO C H H C OH C CH2OPO3 2 H OH Glucose 6-phosphate C C H H HO H C OH H

The Favorskii reaction involves treatment of an a-bromo ketone with base to yield a ring-contracted product. For example, reaction of 2-bromocyclohexanone with aqueous NaOH yields cyclopentanecarboxylic acid. Propose a mechanism. O Br CO2H 1. NaOH 2. H3O+

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. Ether + N2 O O CH2 N N

Ketones react slowly with benzeneselenenyl chloride in the presence of HCl to yield a-phenylseleno ketones. Propose a mechanism for this acid-catalyzed a-substitution reaction. C H C O C6H5SeCl HCl C Se C6H5

As far back as the 16th century, South American Incas chewed the leaves of the coca bush, Erythroxylon coca, to combat fatigue. Chemical studies of Erythroxylon coca by Friedrich Whler in 1862 resulted in the discovery of cocaine, C17H21NO4, as the active component. Basic hydrolysis of cocaine leads to methanol, benzoic acid, and another compound called ecgonine, C9H15NO3. Oxidation of ecgonine with CrO3 yields a keto acid that readily loses CO2 on heating, giving tropinone. O N Tropinone H3C (a) What is a likely structure for the keto acid? (b) What is a likely structure for ecgonine, neglecting stereochemistry? (c) What is a likely structure for cocaine, neglecting stereochemistry?

The final step in an attempted synthesis of laurene, a hydrocarbon isolated from the marine alga Laurencia glandulifera, involved the Wittig reaction shown. The product obtained, however, was not laurene but an isomer. Propose a mechanism to account for these unexpected results. H Laurene (Not formed)

The key step in a reported laboratory synthesis of sativene, a hydrocarbon isolated from the mold Helminthosporium sativum, involves the following base treatment of a keto tosylate. What kind of reaction is occurring? How would you complete the synthesis? A keto tosylate Sativene Base OTos CH3 CH3 CH3 H H H O O H H

Amino acids can be prepared by reaction of alkyl halides with diethyl acetamidomalonate, followed by heating the initial alkylation product with aqueous HCl. Show how you would prepare alanine, CH3CH(NH2)CO2H, one of the twenty amino acids found in proteins, and propose a mechanism for acid-catalyzed conversion of the initial alkylation product to the amino acid. CH3CNHCHCOEt Diethyl acetamidomalonate

Amino acids can also be prepared by a two-step sequence that involves Hell VolhardZelinskii reaction of a carboxylic acid followed by treatment with ammonia. Show how you would prepare leucine, (CH3)2CHCH2CH(NH2)CO2H, and identify the mechanism of the second step.

Heating carvone with aqueous sulfuric acid converts it into carvacrol. Propose a mechanism for the isomerization. Carvacrol

Sodium Pentothal is a short-acting barbiturate derivative used as a general anesthetic and known in popular culture as a truth serum. It is synthesized like other barbiturates (see the A Deeper Look at the end of this chapter), using thiourea, (H2N)2CPS, in place of urea. How would you synthesize Sodium Pentothal? S