Stork and Robinson -- quite a pair!
Today we finished chapter 23 with a look at the Stork Enamine Reaction and the Robinson Annulation Reaction. The Stork is just a glorified Michael Reaction, albeit one that avoids the problem of over-alkylation by eliminating the need for a base. The Robinson is a wonderful Michael/aldol combination that is a chemist's best way to manufacture conjugated cyclohexenes -- this is important in steroid synthesis.
I talked a bit about the exam -- it's heavily mechanistic and a lot like the one from last year. You should be able to handle mechanisms for all of the reactions we've discussed: malonic ester, acetoacetic ester, haloform, aldol, Claisen, Michael, Stork, Robinson, decarboxylation.
Remember that Meagen will be available on Sunday evening from 6 - 8 in the lounge.
The Claisen Reaction
Today we learned the Claisen Reaction. Initially, this is just like an aldol process, but then veers away in two important areas: 1) the addition of the enolate to the C=O does not stop after addition and get protonated, but instead REFORMS the C=O with loss of an alkoxide (just like in normal carboxylic acid derivative chemistry) and 2) the final "product" is deprotonated to give a stabilized enolate, which then MUST be reprotonated by addition of acid. Curiously, this deprotonation is the step that forces the equilibrium in the needed direction.
Just as with aldols, there are mixed and intramolecular (Dieckmann) versions of the Claisen.
We ended with an introduction to the Michael Reaction. On Friday we will continue the theme of addition to conjugated carbonyl systems with looks at the Stork Enamine synthesis and the Robinson Annulation.
Remember, Meagen will be available during her normal Thursday hours and also on Sunday from 6 - 8 in the Althouse Lounge (downstairs).
The Mixed Aldol
Today we saw how to do an aldol reaction with two different starting materials, instead of two different molecules of a single compound serving as nucleophile and electrophile. The trick here is to make sure that only one of the starting materials will be deprotonated by the base. This is carried out by either 1) making sure that only one of the starting materials has an acidic proton or 2) having enormous differences in acidity if both have acidic protons. We looked at examples of both strategies.
We also looked at intramolecular versions of aldol processes and spent some time learning how to draw the products of the ring-forming reactions. An important point here is that not all ring sizes are easily made; we are essentially reduced to making five- or six-membered rings.
The Aldol Reaction
Today we started the aldol reaction. The concept here is that under the correct conditions it is possible to have an aldehyde deprotonated to form an enolate and this enolate can then react as a carbon nucleophile to react with a second equivalent of the aldehyde to create a new C-C bond. All steps are reversible (and in fact the equilibrium is usually against us) so the reaction is driven to completion by having the aldol product undergo an elimination reaction and physically removing water from the mix.
Hopefully, the point was made today that there are lots of competing processes taking place and that, with care, it is possible to wade through them and discard the ones that don't get us anywhere (such as protonation/deprotonation sequences).
Today I have posted PS 11 and a To-Do list for next week.
Remember -- lab reports due next week, modeling due next Friday.
La fin du chapitre 22
Forgive the French; I got excited. Today was spent mainly on the acetoacetic ester synthesis, with an emphasis on the similarity of it to the malonic ester synthesis. Hopefully you can see that they are the same reaction with the difference of the remaining C=O being part of a carboxylic acid or part of a ketone. You should be able to do the mechanism for reactions of this sort, without knowing what they are called.
The beginning of class was a review of the haloform reaction of last week. Check your notes and make sure that you understand what is going on. As always, I don't particularly care if you remember that it is called the haloform reaction and that it forms a carboxylic acid but rather I care that you can figure out the mechanism. It's all about the arrows.
.....pause......
Even though it's fall pause, I'm still hard at work! I've added a few things, including a to-do list for this week, a Need-to-Know for Chapter 23, and a new problem set (#10). Enjoy the rest of your pause!
Malonic Ester Synthesis
The big item today was the misnomer of the title. The Malonic Ester Synthesis does NOT synthesize a malonic ester but rather starts with one and converts an alkyl halide into a carboxylic acid with a two carbon chain extension. Most of class was spent working through the mechanism, which involves deprotonation of the malonic ester (NOTE: use the correct alkoxide as base!), the SN2 reaction to add the alkyl group of the alkyl halide, a double hydrolysis and finally a decarboxylation.
You should be able to work your way through the mechanism; take time to learn the decarboxylation.
Problem Set 9 and the key have been posted to the right; they will give you practice on the Malonic Ester Synthesis and also the Acetoacetic Ester Synthesis, which is our major topic for Wednesday.
Have a great pause!
Enolates!
Today we saw how to increase the nucleophilicity of the alpha-carbon by creating a deprotonated form of an enol called an enolate. Since the enolate has an overall negative charge, it is a stronger nucleophile than the neutral enol. We discussed the necessary strongly reactive nature of the base and mentioned two in particular -- sodium hydride (NaH) and lithium diisopropyl amide (LDA). Both are strong bases and NaH has the added benefit of forming hydrogen gas and bubbling away (preventing the deprotonation from going in reverse). You were left with the task of determining why hydroxide is a bad choice as a base when making enolates.
We saw how the concept of induction led to multiple deprotonations in the haloform reaction, giving what appears to be a strangely oxidized product (a carboxylic acid) from a methyl ketone.
We ended up with a discussion on relative acidities, and noted that a hydrogen on a carbon between two carbonyl groups is much more acidic than a hydrogen on a carbon next to a single carbonyl.
Remember, Friday is a big day -- we will talk about material in Chapter 22.8. The big topics are the Malonic Ester Synthesis and the Acetoacetic Ester Synthesis.
Exam Key posted
The key for exam #2 has been posted. Also, a new video (and we're back to YouTube instead of Google Video) has a couple of pretty neat explosions so you'll want to check it out (link below the WikiMapia at the right).
There is also a to-do list for this week and a new problem set (#8) along with its key, plus the Chapter 22 Need to Know. Extraneous links have been removed from the list of links; everything looks a bit cleaner now.
Exam #2!
Today we had the second exam. Not much to say about it, hopefully I'll have them graded by Friday.
Enols
Today we started to look at enols, with the major focus being a mechanistic view of the keto-enol tautomerism process. We saw how aqueous acid and aqueous base can catalyze the tautomerism. The key here is the realization that water can be an acid, a base, or a nucleophile -- it all depends on the conditions.
Once we saw how enols can be formed, we spent some time on reactions that they can undergo. The template here was the use of the C=C as a nucleophile from Chem 241. Our example was dibromine as the electrophile, we then took it a step further and looked at the venerable Hell-Volhard-Zelinsky reaction, in which a carboxylic acid is converted to an alpha-bromo acid.
Finishing Acid Derivatives
Today we finished Chapter 21; this was the end of material that will be on Monday's exam. The first point was probably the most instructive -- hydrolysis of an amide is EXACTLY the same as hydrolysis of other carboxylic acid derivatives. We also saw examples of biological versions of acid derivatives (thioesters, phosphate esters) and a few examples of reactions involving those species.
The last topic dealt with step-growth polymers. We worked our way through the formation of nylons, starting from diacid halides and diamines. The important point here is that the chemistry is just acid derivative chemistry. In this case, it is the formation of amides from acid halides; all of the chemistry is accessible to those who understand the material in Chapter 21. It is expected that you can determine the nature of the polymer formed in these reactions and be able to draw the structure, using brackets.
A reminder or two: Meagen has moved her hours for tomorrow night back an hour (8 - 10 pm). For the modeling assignment, some of the computers (mostly in the front of the room) use a different release of Spartan (Spartan '04), resulting in a few different screens. Until I get those changes posted, it is better to use the computers at the rear. Just make sure the icon reads "Spartan" and not "Spartan '04" and it'll be OK.
Some additions to the page....
I've placed links to last year's exam #2 over to the right, along with a new Wikimapia and GoogleVideo chemistry video of the week. The map shows Earlham College's campus in Richmond, IN (where I taught from 1987 - 1989). The chemistry/biology/psychology building is the white structure at the very top of the picture. The video is one of those Mentos/Diet Coke explosions -- not the best one I've seen but it's still fun to watch.
Continuing with Acid Derivatives
We kept going with acid derivative chemistry today, with the major focus on acid halides. We looked at reactions to convert them to esters, amides, acids (hydrolysis) and alcohols. The major point was that all of these reactions are exactly the same thing! That is the big secret of organic chemistry; once you figure that part out all the rest comes more easily.
At the end I had everyone work on a Fischer esterification reaction and pointed out that for the next exam I would expect that question to take about 5 minutes.
This morning I sent out an e-mail with the assignments for the modeling exercise and a link to the structures. I cut back on the number of possibilities, ultimately only assigning one of just three molecules, all of which require only 8 - 10 minutes of processing time.
