24 • Additional Problems
24 • Additional Problems
The following compound contains three nitrogen atoms. Rank them in order of increasing basicity.
Name the following amine, including R,S stereochemistry, and draw the product of its reaction with excess iodomethane followed by heating with Ag2O (Hofmann elimination). Is the stereochemistry of the alkene product Z or E? Explain.
Which nitrogen atom in the following compound is most basic? Explain.
Substituted pyrroles are often prepared by treatment of a 1,4-diketone with ammonia. Propose a mechanism.
3,5-Dimethylisoxazole is prepared by reaction of 2,4-pentanedione with hydroxylamine. Propose a mechanism.
Chlorophyll, heme, vitamin B12, and a host of other substances are biosynthesized from porphobilinogen (PBG), which is itself formed from condensation of two molecules of 5-aminolevulinate. The two 5-aminolevulinates are bound to lysine (Lys) amino acids in the enzyme, one in the enamine form and one in the imine form, and their condensation is thought to occur by the following steps. Use curved arrows to show the mechanism of each step.
Choline, a component of the phospholipids in cell membranes, can be prepared by SN2 reaction of trimethylamine with ethylene oxide. Show the structure of choline, and propose a mechanism for the reaction.
The antitumor antibiotic mitomycin C functions by forming cross-links in DNA chains.
α-Amino acids can be prepared by the Strecker synthesis, a two-step process in which an aldehyde is treated with ammonium cyanide followed by hydrolysis of the amino nitrile intermediate with aqueous acid. Propose a mechanism for the reaction.
One of the reactions used in determining the sequence of nucleotides in a strand of DNA is reaction with hydrazine. Propose a mechanism for the following reaction, which occurs by an initial conjugate addition followed by internal amide formation.
When an α-hydroxy amide is treated with Br2 in aqueous NaOH under Hofmann rearrangement conditions, loss of CO2 occurs and a chain-shortened aldehyde is formed. Propose a mechanism.
The following transformation involves a conjugate nucleophilic addition reaction (Section 19.13) followed by an intramolecular nucleophilic acyl substitution reaction (Section 21.2). Show the mechanism.
Propose a mechanism for the following reaction:
One step in the biosynthesis of morphine is the reaction of dopamine with p-hydroxyphenylacetaldehyde to give (S)-norcoclaurine. Assuming that the reaction is acid-catalyzed, propose a mechanism.
Histamine, whose release in the body triggers nasal secretions and constricted airways, has three nitrogen atoms. List them in order of increasing basicity and explain your ordering.
Synthesis of Amines
How might a reductive amination be used to synthesize ephedrine, an amino alcohol that was widely used for the treatment of bronchial asthma?
Reactions of Amines
Phenacetin, a substance formerly used in over-the-counter headache remedies, has the formula C10H13NO2. Phenacetin is neutral and does not dissolve in either acid or base. When warmed with aqueous NaOH, phenacetin yields an amine, C8H11NO, whose 1H NMR spectrum is shown. When heated with HI, the amine is cleaved to an aminophenol, C6H7NO. What is the structure of phenacetin, and what are the structures of the amine and the aminophenol?
Fill in the missing reagents a–e in the following scheme:
Oxazole is a five-membered aromatic heterocycle. Would you expect oxazole to be more basic or less basic than pyrrole? Explain.
Protonation of an amide using strong acid occurs on oxygen rather than on nitrogen. Suggest a reason for this behavior, taking resonance into account.
What is the structure of the compound with formula C8H11N that produced the following IR spectrum?
Fill in the missing reagents a–d in the following synthesis of racemic methamphetamine from benzene.
Cyclopentamine is an amphetamine-like central nervous system stimulant. Propose a synthesis of cyclopentamine from materials of five carbons or less.
Atropine, C17H23NO3, is a poisonous alkaloid isolated from the leaves and roots of Atropa belladonna, the deadly nightshade. In small doses, atropine acts as a muscle relaxant; 0.5 ng (nanogram, 10–9 g) is sufficient to cause pupil dilation. On basic hydrolysis, atropine yields tropic acid, C6H5CH(CH2OH)CO2H, and tropine, C8H15NO. Tropine is an optically inactive alcohol that yields tropidene on dehydration with H2SO4. Propose a structure for atropine.
Propose a structure for the product with formula C9H17N that results when 2-(2-cyanoethyl)cyclohexanone is reduced catalytically.
Tyramine is an alkaloid found, among other places, in mistletoe and ripe cheese. How would you synthesize tyramine from benzene? From toluene?
Heating the diazonium carboxylate results in the formation of CO2, N2, and an intermediate that reacts with 1,3-cyclopentadiene to yield the following product:
What is the structure of the intermediate, and what kind of reaction does it undergo with cyclopentadiene?
Cyclooctatetraene was first synthesized in 1911 by a route that involved the following transformation:
How might you use the Hofmann elimination to accomplish this reaction? How would you finish the synthesis by converting cyclooctatriene into cyclooctatetraene?
4-Dimethylaminopyridine (DMAP) acts as a catalyst in acyl transfer reactions. DMAP’s catalytic activity stems from its nucleophilic character at the pyridine nitrogen, not the dimethylamino group. Explain this behavior, taking resonance into account.