Chapter 18.Carboxylic Acids and Their Derivatives

1.Relative amounts of resonance stabilization and relative reactivity of acid chlorides, esters, carboxylic acids, amides, and carboxylate anions. Be able to write resonance structures and rationalize the relative extents of resonance stabilization. Be familiar with the use of thionyl chloride to prepare acid chlorides.

2.Be able to write the detailed mechanisms of acid catalyzed and base promoted hydrolysis of esters. Be able to explain what essentially is happening in each step of the mechanism. Know that these reactions are net substitutions but that they proceed via addition/elimination. Be able to write the mechanism for acid catalyzed esterification. Where does the equilibrium position lie and why? How can the equilibrium be displaced? Why is there no useful base catalyzed or base promoted esterification reaction? What is another name for base promoted hydrolysis of esters?Explain why base promoted ester hydrolysis goes to completion . Be able to write the mechanism for acid catalyzed transesterification.

3. Be able to write the mechanism of acid and base promoted hydrolysis of amides. Why are these reactions promoted rather than catalyzed?Why are amides weaker bases than amines. Where are amides protonated (which atom) and why? Why is the nitrogen atom of an amide trigonally hybridized rather than pyramidally hybridized as it is iin an amine?

Special Topic I: Step Growth Polymerization

1.Be able to write the names and structures of the monomers from which Nylon 6,6 is prepared and also the repeating structure of the polymer. Be able to write the equation for the first step of the polymerization and to show how further reaction leads to polymerization. Why is this polymerization termed condensation polymerization? What type of linkage bonds the monomer units together? Why is it called step growth polymerization (as opposed to what other type of polymerization?)?

2.From what monomer is Nylon 6 prepared (name and structure). Be able to write the repeating structure of the polymer and to compare it regiochemically with Nylon 6,6. What is the difference between copolymerization and simple polymerization(i.e. homopolymerization)?

3.Assume that a given monomer is polymerized partially, but that the polymerization is interrupted after only a short reaction time so that only , say, 10% of the monomer has been consumed (90% of the original monomer remains).Considering the 10% of the monomer which has been converted to product, compare the nature of the product when the polymerization is step growth vs. when the polymerization is of the chain growth type.

Chapter 19. Beta Dicarbonyl Compounds

1.Why are beta dicarbonyl compounds especially acidic (pKa = 9-11). Use resonance theory to support your answer. Why do they contain large amounts of the enol form( again, resonance theory should be used to support your answer)?

2.Be able to write the detailed mechanism of the Claisen ester condensation. Rationalize the observation that it is base promoted rather than base catalyzed. How is this important in the thermodynamics of the reaction? Explain why the reaction fails if the reactant ester has only a single alpha type hydrogen.Be familiar with the intramolecular and crossed Claisen condensations.

3. Know the uses and limitations of the acetoacetic ester and malonic ester syntheses. Be familiar with the cyclic mechanism of the decarboxylation of beta keto acids and malonic acids. What is the thermodynamic driving force for this reaction? What is the initial reaction product? Why is this reaction so facile, when the decarboxylation of simple carboxylic acids is very difficult? Be familiar with the synthesis of cyclic ketones and acids using the variant of the acetoacetic ester and malonic ester syntheses which uses a dihalide.

4.Be able to recognize the structure of barbituric acid and to show how it is synthesized. Be able to sketch syntheses of Veronal and phenobarbital ( the latter requires a special version of the Claisen ester condensation).

Chapter 20 . Amines

1. Nomenclature (common, IUPAC, and substituent) of amines. What is the hybridization of nitrogen in amines? This can be described as either tetrahedral or (what)? Be able to explain why this hybridization state is preferred over the planar hybridization state ( the lone pair on nitrogen prefers to be in the sp3 AO, which is of lower energy than a pure 2p orbital-- the doubly occupied orbital is especially important energetically because the number of electrons in it is approximately twice that in the other Nitrogen AO's). What type of carbon intermediate is isoelectronic with ammonia (carbanion)? How can the energy difference between the pyramidal and planar states of an amine be measured experimentally (activation barrier to racemization). Explain why amines can be chiral but usually racemize quickly. What is the structural requirement for an amine to be chiral? Are chiral ammonium ions possible? Are they subject to racemization by an umbrella type inversion such as occurs with amines? Why or why not?

2. Compare a primary or secondary amine with an alcohol in terms of acidity. What about tertiary amines, in terms of their acidity?

3. Are amines stronger as bases or as acids? Compare the basicity of amines with that of alcohols. Which is more basic and why? Which is the stronger base ,methylamine or ammonia? Why? Which is the stronger acid, methylammonium ion or ammonium ion? Why? What is the order of basicity of amines ( ammonia vs primary vs. secondary vs. tertiary ) in the gas phase? Explain. What is the order of basicity of amines in solution? Explain.

4. Is aniline a stronger or weaker base than ,say, ethylamine? Explain, using resonance theory. Be sure to consider both sides of the equation ( i.e., both aniline and the anilinium ion). Which is the stronger base, an amine or an amide? Explain. Because the basicity of nitrogen is so strongly affected be the amide carbonyl group, what rather surprising result occurs when an amide is protonated by strong acid? Compare the relative hybridizations of N in amines and amides and explain any differences.

5.Be familiar with various methods of preparing amines. What is the inherent problem with alkylation and how can this problem sometimes be overcome( multiple alkylations; large excess of starting amine or ammonia).Be familiar with the Gabriel synthesis using phthalimide and the strategy which allows it to avoid multiple alkylation.Be familiar with the reduction of azides and of nitro compounds as methods of synthesizing amines ( you will need to know which reductants are necessary in each case).

6. Be familiar in a synthetic sense with the reactions of aliphatic and aromatic amines with nitrous acid to give dizaonium ions. Be able to write resonance structures for the diazonium ions and to explain why arene diazonium ions are relatively much more stable than aliphatic diazonium ions. Know what the fate of aliphatic diazonium ions is and why ( related to the excellence of dinitrogen as a leaving group,giving substitution and elimination reactions, often involving carbocations). Be familiar with the use of arene diazonium ions in the Sandmeyer reaction.

7.Be able to write the mechanism of the diazo coupling reactions of arenediazonium ions with dimethylaniline and with phenol (really with phenoxide ion).Know the structure of diazo compounds and the theoretical basis for their color. Why are ionic groups needed before a colored azo compound can be a suitable dye? What ionic group is usually employed?

8. Be able to discuss the E2 elimination which we call the Hoffmann elimination and to develop a TS model. Be able to use this model to rationalize the contrasting regiochemistry in these eliminations and those seen in the eliminations of alkyl halides?

Chapter 21. Phenols

1. Be able to discuss the theoretical basis for the enhanced acidity of phenols as compared to simple alcohols. How can phenols be simply separated from a mixture containing both a carboxylic acid and a nonpolar molecule like cyclohexanone, along with phenol. Explain why this is possible?

2.Be familiar with the Kolbe reaction and its use in the synthesis of aspirin.