CH 618B (Majors)
Exam #3 Emphasis Topics
1. Aldehyde and Ketone IUPAC nomenclature.
2. Why is the direct reduction of carboxylic acids to aldehydes by LAH not feasible? What is the only product obtainable in good yield in such a reaction? Why are acid chlorides a much better choice for reduction to an aldehyde? Why is LAH an unsatisfactory reductant for the conversion of an acid chloride to an aldehyde? What reagent is appropriate and why is it superior to LAH for this purpose?
3. What reagent is appropriate for the reduction of esters to aldehydes? Write the mechanism of the reaction and explain why this strategy works. Explain why ester functions are more thermodynamically stable and generally less reactive than ketone carbonyl groups?
4.What functional group does permit a direct reduction to the aldehyde function (after hydrolysis)? Explain why reduction stops at this stage.
5. Recognize the relative order of thermodynamic stability of aldehyde, ketone, ester, carboxylic acid, and acid chloride carbonyl groups and be able to explain the order based upon substituent effects upon the carbocation character of the respective carbonyl groups.
6. Be able to write the detailed mechanism for the acid catalyzed hydration of an alkyne (e.g., a terminal alkyne); also be able to write the mechanism for the acid catalyzed tautomerization of the initially formed enol to the keto form; be able to explain why the equilibrium lies on the keto side.
7.What reagent permits the conversion of an acid chloride to a ketone? How is the reagent prepared? Explain why a Grignard reagent or organolithium compound would not be effective for this purpose.
8. What functional group which has the same oxidation level as a carboxylic acid is readily converted to a ketone function without the problem of addition of a seond mole of Grignard reagent? Explain why this procedure is effective.
9.Write the detailed mechanism for both acid and base catalyzed hydration of a ketone. Indicate which side of the equilibrium is favored and explain why. Is this corresponding equilibrium for an aldehyde more or less favorable than for a ketone. Why?
10.Be able to write the detailed mechanism for acid and base catalyzed hemiacetal formation .Also, write the mechanism for the acid catalyzed conversion of a hemiacetal to an acetal. Why is the base catalyzed process ineffective? What kind of substitution mechanism is involved in the acid catalyzed process. Explain why this mechanism is particularly favorable and why the alternate substitution mechanism is not. Under what conditions are acetals stable? Be familiar with cyclic acetal formation and the reason it is especially favorable. Also, be familiar with the use of acetals and cyclic acetals as protecting groups in synthesis.
11. In a purely synthetic sense, you should know how to reduce carbonyl functions directly to the alkane moiety ( CH2) by the thioacetal and Wolff-Kishner methods ( no mechanisms).Know the general scheme for the conversion of carbonyl double bonds to imine double bonds (addition and elimination). Be familiar with cyanohydrin formation, including the mechanism, and the synthetic uses of cyanohydrins.
12. The Wittig reaction. Formation of Wittig reagents. The mechanism of the reaction with aldehydes or ketones.
1. Enolates: Mechanism of their formation; resonance treatment and charge distribution; relationship to the enol and keto forms.
2. Mechanism of racemization and halogenation of ketones; the nucleophilic reactivity of enols and enolates (which is more reactive); why are enols more reactive than simple alkenes toward electrophiles.
3. Skip the haloform reaction and the iodoform test.
4. The Aldol addition: mechanism of the base catalyzed reaction (omit acid catalyzed mechanism); be able to predict the structures of the products from aldehydes other than acetaldehyde; be familiar with the intramolecular aldol cyclization; crossed aldols-why they usually don't work and when they can be used.
5. Mechanism of dehydration of aldols to unsaturated carbonyl compounds; resonance stabilization of the latter and driving force for dehydration;hydroxide ion as a leaving group; nucleophilic additions to unsaturated carbonyl compounds ( 1,2 and 1,4).
6.Formation of LDA and use to form lithium enolates; alkylation of ketones via enolates; kinetic vs. thermodynamic control of enolate formation; silyl ethers as protecting groups.