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?
 

Topic 45: Synthesis of a quaternary ammonium salt by SN2 displacement involving an alkyl halide

45.1What is a quaternary ammonium salt?
 
45.2Why are quaternary ammonium salts useful? (When have use used these in lab? Why?)
 
45.3Why is direct SN2 reaction of an amine with an alkyl bromide not generally useful?
 
45.4Why does this work if what you want to form is a quaternary ammonium salt?
 

Topic 46: Synthesis of amines

46.1How can the reaction of ammonia with a primary alkyl halide to form a primary alkyl halide be designed to be successful?
 
46.2Is the use of a huge excess of ammonia to produce a primary amine a kinetic or thermodynamic strategy?
 
46.3How did Siegmund Gabriel (in 1887!) solve the problem of overalkylation in the synthesis of primary amines?
 
46.4What reagents can be used to reduce a nitro compound to an amine?
 
46.5What type of amine (primary, secondary, or tertiary) can be made this way?
 
46.6What two carboxylic acid derivatives can be reduced to amines using LiAlH4?
 
46.7What type of amine (primary, secondary, or tertiary) can be made this way?
 
46.8What is reductive amination?
 
46.9What is the formula of sodium cyanoborohydride? Why is it necessary to use this very mild reducing agent for reductive amination?
 

Topic 47: Amine basicity

47.1Which is more basic, ethylamine or diethylamine? Why?
 
47.2Which is more basic, ethylamine or acetamide? Why?
 
47.3How do you explain the difference in basicity of pyridine and piperidine?

 
47.4What are the approximate pKa values of diisopropylamine and aniline? How do you explain the difference?
 

Topic 48: Diazonium salts and azo compounds

48.1What is an aryl diazonium salt?
 
48.2How are aryl diazonium salts made?
 
48.3What are they good for?
 
48.4What is hypophosphorous acid, and why is its reaction with an aryl diazonium salt useful?
 
48.5What is azo coupling?
 
48.6How does that work?
 
48.7What are some limitations of azo coupling?
 
48.8What industry has particularly taken advantage of this chemistry?
 
48.9What health/environmental issues are particularly concerning about azo compounds? (see, for example, this report)
 

Topic 49: Olefin metathesis

49.1What is an olefin?
 
49.2What is a carbene? (see Section 24.4, first paragraph only)
 
49.3What is a transition metal—carbene complex?
 
49.4What, effectively, does olefin metathesis do?
 
49.5What is ring closing metathesis, and why is it so cool?
 
49.6What is the generally accepted four-step catalytic cycle mechanism for olefin metathesis, starting with a transition metal—carbene complex?
 

Topic 50: Organometallic reactions involving palladium

50.1What is a ligand?
 
50.2What is a precatalyst?
 
50.3What is ligand dissociation?
 
50.4What is ligand exchange?
 
50.5What is transmetalation?
 
50.6What is oxidative addition? (And where have you seen it before?)
 
50.7What is reductive elimination?
 

Topic 51: Suzuki coupling (aka Suzuki-Miyaura reaction)

51.1What is a vinylboronic ester and how is it made?
 
51.2What is an arylboronic ester, and how is it made?
 
51.3What two types of compounds are coupled in a Suzuki coupling?
 
51.4What does it mean to say that the Suzuki-Miyaura reaction with a vinyl halide is stereospecific?
 
51.5What is the generally accepted four-step catalytic cycle mechanism for a Suzuki coupling, starting with the active catalyst, Pd(PPH3)2, written simply as “Pd0”? [indicate oxidation state of Pd at each point in the mechanism]
 
51.6What are the names of the four steps in the generally accepted mechanism of a Suzuki coupling, in order.
 
51.7What is the role of NaOH in this reaction?
 

Topic 52: The Heck reaction

52.1What is a π complex?
 
52.2What is alkene insertion?
 
52.3What is β-hydride elimination in organometallic chemistry?
 
52.4What two types of compounds are coupled in a Heck reaction?
 
52.5What is the generally accepted six-step catalytic cycle mechanism for the Heck reaction, starting with the active catalyst written simply as “Pd0”? [Indicate oxidation state of Pd at each point in the mechanism. For example, Pd0, PdII, PdIV, using Roman numerals for oxidation state.]
 
52.6What are the names of the six steps in the generally accepted mechanism of the Heck reaction, in order?
 
52.7What two steps do the Heck reaction and Suzuki coupling have in common?
 
52.8The Heck reaction generally only works with ethene and with alkenes that have an electron withdrawing group. What do these two have in common? The real question is this: Why doesn‘t the Heck reaction generally work with a simple alkene such as 1-hexene? [Hint: The answer to this is in mechanistic step #4; what is “chain walking”?]
 
119 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)