Topic 37: Reaction at the alpha carbon: enols and enolates

37.1What is an enol?
 
37.2What is an enolate?
 
37.3How many times more acidic is 2,4-pentanedione than 2-pentanone?
 
37.4How might that be relevant to this discussion?
 
37.5Tautomerization can be catalyzed either by acid or base. What is the mechanism of tautomerization in each case?
 
37.6What other compounds, besides ketones and aldehydes, can be deprotonated to form enolate-like species?
 
37.7What is the most common base used to make enolates?
 
37.8Why is it better than hydroxide?
 
37.9Why is it better than MeLi?
 
37.10What does LDA stand for? Structure?
 
37.11Why might it be most common to use LDA at such a low temperature as −78 C?
 
37.12What is the difference between kinetic and thermodynamic control?
 
37.13What is the general way to make a “kinetic” enolate?
 
37.14The standard way to equilibrate a pair of enolates is to deprotonate the ketone with LDA at −78 C using slightly less than one equivalent of base and then to just let the reaction warm up to room temperature. Why would it be important to have just a little bit of unreacted ketone present when this warming occurs? How does that accomplish equilibration?
 
37.15Why/when would it be important to not expose a ketone to strong acid or strong base?
 
37.16How could this process work in your favor, if you were a synthetic organic chemist?
 

Topic 38: Reactions of enols and enolates with molecular bromine, chlorine, and iodine

38.1Molecular bromine (Br2) reacts with double bonds. What is the mechanism of that reaction?
 
38.2In the presence of a trace of acid, ketones and aldehydes establish an equilibrium between keto and enol forms that usually involves a very small percentage of enol. How does this explain the acid-catalyzed reaction of Br2 with ketones and aldehydes?
 
38.3What are two uses of α-bromoketones?
 
38.4What is initial product of reaction of I2 with a ketone in the presence of base?
 
38.5What is the limitation of this reaction?
 
38.6When can this limitation work for us to do something useful?
 

Topic 39: Reactions of enolates with alkyl bromides: direct alkylation

39.1What is the most common strong nonnucleophilic base used to irreversibly deprotonate a ketone?
 
39.2Why is the reaction of an enolate with an alkyl bromide generally carried out at −78 C?
 
39.3Does this procedure produce the kinetic product or the thermodynamic product?
 
39.4How would we go about finding the original journal article for a reaction such as the following that you read about in a book and want to know more about? [Hint: Have you used SciFinder?]

 
39.5What are two major issues in trying to alkylate ketones using enolates? How does the use of 1,3-dicarbonyl compounds address at least one of these issues?
 
39.6What are the structures of the 1,3-dicarbonyl compounds 2,4-pentanedione, ethyl 3-oxobutanoate, and diethyl malonate?
 
39.7Why is sodium ethoxide (NaOEt) a suitable base for the irreversible deprotonation and alkylation of 1,3-dicarbonyl compounds?
 
39.8After alkylation of ethyl 3-oxobutanoate with benzyl chloride, aqueous NaOH is added, the reaction is stirred for a while, then acidified with HCl and heated. What happens? What is the structure of the aromatic compound produced in this reaction?
 

Topic 40: The aldol reaction and the aldol condensation

40.1What is a β-hydroxycarbonyl compound?
 
40.2What is the aldol reaction?
 
40.3What is the mechanism of the aldol reaction of acetone in aqueous NaOH?
 
40.4Is an aldol reaction catalytic in base, or does it require a full equivalent?
 
40.5What is a “condensation” reaction?
 
40.6What is the aldol condensation?
 
40.7Why are aldol condensations generally more successful than aldol reactions?
 
40.8What is the E1cb mechanism?
 
40.9You learned last semester that OH− is not a leaving group. That is generally true. So why does the aldol condensation work?
 
40.10Why don‘t we generally use acetone as a solvent in organic reactions?
 

Topic 41: Crossed and intramolecular aldol reactions and condensations

41.1What does “crossed aldol” mean?
 
41.2What is a limitation of the crossed aldol condensation using hydroxide as a base? (What must be true for it to be useful?)
 
41.3How can we direct the crossed aldol reaction to go the way we want it to if both reactants have α hydrogens?
 
41.4How many stereocenters can be created with a directed aldol reaction? [hint]
 
41.5What is the salient feature of an intramolecular aldol reaction that makes it so valuable in organic synthesis?
 

Topic 42: The Claisen condensation

42.1What is a β-keto ester?
 
42.2What is the Claisen condensation (aka Claisen reaction)?
 
42.3What makes the Claisen condensation a "condensation"?
 
42.4What is the mechanism of the Claisen condensation involving ethyl acetate and sodium ethoxide?
 
42.5Why is sodium ethoxide preferred over NaOH or NaOMe in this reaction?

 
42.6Why does a Claisen condensation require a full equivalent of sodium ethoxide? Why not two?
 
42.7Why do you think we generally use hexanes and ethyl ether rather than ethyl acetate for work-ups in the organic lab?
 

Topic 43: Reactions related to Claisen condensations

43.1What is a crossed Claisen condensation?
 
43.2Compare the pKa values of acetone and ethyl acetate. Which is more acidic? Why is that? How does that relate to the reaction of a 5-keto ester with base?
 
43.3Under what circumstances might we expect a crossed Claisen condensation to be successful?
 
43.4What is the salient feature of an intramolecular Claisen condensation that makes it so valuable in organic synthesis?
 
43.5 Following up a Dieckmann condensation with aqueous base, acid, and heating, what do you get?
 
43.6What's with all these names?? What the heck. What is the Thorpe-Ziegler condensation?
 
43.7Why do organic chemists give peoples‘ names to reactions?
 
43.8Names are not particularly important here. What is important is ketones, aldehydes, and esters all undergo condensation reactions in the presence of base either with carbonyl compounds of their own kind or otherwise. What are examples of all six pairings of these three compound types?
 

Topic 44: Michael addition and Robinson annulation

44.1What‘s the twist on this story that makes for a Michael reaction?
 
44.2What is a Robinson annulation?
 
44.3What does “tandem” mean in the context of chemical reactions? (It is a little different from the general English language definition.)
 
44.4What two other named reactions did Robinson link together for his namesake annulation?
 
44.5In what field of organic synthesis has the Robinson annulation been of particular service?
 
65 questions
472 questions for Organic II

472 Questions for Organic II

Dearest Student. This web page is a set of questions I call Detailed Intended Learning Outcomes For Organic Chemistry (Part II). Some time ago I asked myself, "Bob, what do you think are the key questions that you hope students will be able to answer after taking Chemistry 248 at St. Olaf College?" So here you have them. Some are very simple; some require more thought. All are good questions to be thinking about as you read, discuss, and master the practical aspects of organic chemistry. They are discussion starters and review tips. There are no answers here (though there are some clues). The questions are here to help you focus on what's important (to me, at least!) and organize your learning process. The questions are grouped into topics. Bite-size chunks. Take them a few at a time. Don't feast on them all at one sitting!

(preliminary version 2021.01.15 feeback: Bob Hanson)