21 • Additional Problems
21 • Additional Problems
The following structure represents a tetrahedral alkoxide-ion intermediate formed by addition of a nucleophile to a carboxylic acid derivative. Identify the nucleophile, the leaving group, the starting acid derivative, and the ultimate product (green = Cl).
Electrostatic potential maps of a typical amide (acetamide) and an acyl azide (acetyl azide) are shown. Which of the two do you think is more reactive in nucleophilic acyl substitution reactions? Explain.
Pivalic mixed anhydrides are often used to form amide bonds between amino acids. Unlike with a symmetrical anhydride, this reaction is highly regioselective, with the nucleophile adding only to the amino-acid carbonyl. Provide the complete mechanism for the following reaction and explain the regioselectivity.
Fats are biosynthesized from glycerol 3-phosphate and fatty-acyl CoA’s by a reaction sequence that begins with the following step. Show the mechanism of the reaction.
Treatment of an α-amino acid with DCC yields a 2,5-diketopiperazine. Propose a mechanism.
Succinic anhydride yields the cyclic imide succinimide when heated with ammonium chloride at 200 °C. Propose a mechanism for this reaction. Why do you suppose such a high reaction temperature is required?
The hydrolysis of a biological thioester to the corresponding carboxylate is often more complex than the overall result might suggest. The conversion of succinyl CoA to succinate in the citric acid cycle, for instance, occurs by initial formation of an acyl phosphate, followed by reaction with guanosine diphosphate (GDP, a relative of adenosine diphosphate [ADP]) to give succinate and guanosine triphosphate (GTP, a relative of ATP). Suggest mechanisms for both steps.
One step in the gluconeogenesis pathway for the biosynthesis of glucose is the partial reduction of 3-phosphoglycerate to give glyceraldehyde 3-phosphate. The process occurs by phosphorylation with ATP to give 1,3-bisphosphoglycerate, reaction with a thiol group on the enzyme to give an enzyme-bound thioester, and reduction with NADH. Suggest mechanisms for all three reactions.
Bacteria typically develop a resistance to penicillins and other β-lactam antibiotics (see Chemistry Matters at the end of this chapter) due to bacterial synthesis of β-lactamase enzymes. Tazobactam, however, is able to inhibit the activity of the β-lactamase by trapping it, thereby preventing a resistance from developing.
The following reaction, called the benzilic acid rearrangement, takes place by typical carbonyl-group reactions. Propose a mechanism (Ph = phenyl).
In the iodoform reaction, a triiodomethyl ketone reacts with aqueous NaOH to yield a carboxylate ion and iodoform (triiodomethane). Propose a mechanism for this reaction.
Naming Carboxylic Acid Derivatives
Nucleophilic Acyl Substitution Reactions
The following reactivity order has been found for the saponification of alkyl acetates by aqueous NaOH. Explain.
CH3CO2CH3 > CH3CO2CH2CH3 > CH3CO2CH(CH3)2 > CH3CO2C(CH3)3
tert-Butoxycarbonyl azide, a reagent used in protein synthesis, is prepared by treating tert-butoxycarbonyl chloride with sodium azide. Propose a mechanism for this reaction.
The step-growth polymer nylon 6 is prepared from caprolactam. The reaction involves initial reaction of caprolactam with water to give an intermediate open-chain amino acid, followed by heating to form the polymer. Propose mechanisms for both steps, and show the structure of nylon 6.
Qiana, a polyamide fiber with a silky texture, has the following structure. What are the monomer units used in the synthesis of Qiana?
What is the structure of the polymer produced by treatment of β-propiolactone with a small amount of hydroxide ion?
Polyimides with the structure shown are used as coatings on glass and plastics to improve scratch resistance. How would you synthesize a polyimide? (See Problem 21-39.)
Propose a structure for a compound, C4H7ClO2, that has the following IR and 1H NMR spectra:
The following reactivity order has been found for the basic hydrolysis of p-substituted methyl benzoates:
Y=NO2 > Br > H > CH3 > OCH3
How can you explain this reactivity order? Where would you expect Y=CN, Y=CHO, and Y=NH2 to be in the reactivity list?
When a carboxylic acid is dissolved in isotopically labeled water, the label rapidly becomes incorporated into both oxygen atoms of the carboxylic acid. Explain.
Treatment of a carboxylic acid with trifluoroacetic anhydride leads to an unsymmetrical anhydride that rapidly reacts with alcohol to give an ester.
Butacetin is an analgesic (pain-killing) agent that is synthesized commercially from p-fluoronitrobenzene. Propose a synthesis.
Phenyl 4-aminosalicylate is a drug used in the treatment of tuberculosis. Propose a synthesis of this compound starting from 4-nitrosalicylic acid.
N,N-Diethyl-m-toluamide (DEET) is the active ingredient in many insect-repellent preparations. How might you synthesize this substance from m-bromotoluene?
Tranexamic acid, a drug useful against blood clotting, is prepared commercially from p-methylbenzonitrile. Formulate the steps likely to be used in the synthesis. (Don’t worry about cis–trans isomers; heating to 300 °C interconverts the isomers.)
One frequently used method for preparing methyl esters is by reaction of carboxylic acids with diazomethane, CH2N2.
The reaction occurs in two steps: (1) protonation of diazomethane by the carboxylic acid to yield methyldiazonium ion, CH3N2+, plus a carboxylate ion; and (2) reaction of the carboxylate ion with CH3N2+.
Propose a structure for the compound with the formula C19H9NO2 and the following IR and NMR spectra
Draw the structure of the compound that produced the following spectra. The infrared spectrum has strong bands at 1720 and 1738 cm–1.
Epoxy adhesives are prepared in two steps. SN2 reaction of the disodium salt of bisphenol A with epichlorohydrin forms a “prepolymer,” which is then “cured” by treatment with a triamine such as H2NCH2CH2NHCH2CH2NH2.
Draw structures to show how addition of the triamine results in a strengthening of the polymer.