Acid Derivatives, Part 1
Today we started to talk about derivatives of carboxylic acids. We looked at the range of derivatives and spent a long time on explaining the relative reactivities. Hopefully, everyone understands the concept that relative reactivity has everything to do with the nature of the leaving group. We spent a brief time on how acid halides and anhydrides are formed from carboxylic acids and then finished up by looking at the Fisher Esterification reaction -- a complete mechanism which (surprise!) depends on the protonation of the O in a C=O bond to activate the C towards attack by a nucleophile. We then also saw that this process is reversible, allowing a chemist to make an ester from an acid, or an acid from an ester. I left you with the hope that you would stare at the mechanism over the weekend until you understood it.
As promised, a new problem set has been posted, along with next week's to-do list and the modeling instructions.
The End of Carboxylic Acids
Today was the end of Chapter 20. We talked about how to prepare carboxylic acids and noted two important new methods -- hydrolysis (reaction with water) of nitriles and reaction of Grignards with carbon dioxide. Being able to work through the mechanism of acid hydrolysis of a nitrile is a useful skill; we spent the last 12 - 15 minutes of class working on it in groups.
We also saw two examples of the astounding reactivity of lithium aluminum hydride -- when it reacts with a carboxylic acid to form an alcohol and when it reacts with a nitrile to form an amine. In both cases the hydride source continues to attack even though there is a negative charge!
At the beginning of class, I talked a bit about the modeling projects and gave a brief overview of the kinds of things that you will have to do. By the beginning of next week each student will receive an e-mail (to their Dickinson address) containing an attached file. That file will be the starting material for a Claisen rearrangement that will be studied. The instructions will be posted shortly. I mentioned that lab time would be a good time to work on these.
Chapter 21 will be the topic for the next three days. Planned coverage is Friday: 21.1 - 3; Monday: 21.4 - 5; Wednesday: 21.6 - 8. Problem set 6 and the Chapter 21 Need to Know will be posted to the right and on the web site.
Start of Carboxylic Acids
Today we started talking about carboxylic acids. Most of the discussion was centered around factors that control the acidity of the carboxylic acid. There were two major ways to look at this: Induction and resonance. Induction was defined as a "through-space interaction" in which electron-withdrawing groups on carbons near to the carboxyl fragment could induce a partial positive charge on a carbon atom, which would in turn "drag" the negative charge of the conjugate base towards itself, thus increasing the volume of space occupied by the charge. This increases the stability of the conjugate base, leading to increased acidity of the carboxylic acid itself. Substituted benzoic acids were used to demonstrate how resonance could play a role; electron-withdrawing groups placed a partial positive charge next to the carboxylate and therefore stabilized the conjugate base (thereby increasing the acidity of the acid). Electron donating groups had the opposite effect.
The first 20 minutes of class dealt with finishing up the enamine reaction started last Friday. We showed how to go "backwards" and do a hydrolysis of the enamine, ending up with the carbonyl compound and starting secondary amine. It will be important to be able to show mechanisms in both directions.
Wittigs and More!
Today was the end of Chapter 19. We talked about the Wittig reaction -- remember that in the end, it is just a fancy carbon nucleophile. The difficult parts of the Wittig are the formation of the four-membered ring and the corresponding reorganization to the products, so pay attention to those parts and make sure that you can push the arrows and understand the results.
We also talked about 1,2- v. 1,4-addition to conjugated C=O systems. This is a relatively simple concept as long as you remember to do the keto-enol tautomerism at the end.
The
To Do list for next week has been posted. Coverage for Chapter 20: Monday sections 1 - 5, 10 and Wednesday sections 6 - 9.
Have a great weekend!
New Fun Stuff
A new Google Video Chemistry Video of the Week is up -- this one is a bad rap video, filmed in Cleveland, of all places....but it has a great chemistry theme. Sticking with the Cleveland thing, the Wikimapia site is now the 2700 block of Hampshire Road in Cleveland Heights, OH. I lived in first building to the right of the parking lot for two years while I was a post-doc at Case Western Reserve University. If you zoom back once or twice, you'll see Lakeview Cemetery and the tomb of President James Garfield. Zooming back a bit more and heading west will take you to the waterfront, including the Rock & Roll Hall of Fame.
Imines and Enamines
Today we slid sideways into nitrogen nucleophiles reacting with C=O. We used the alcohol reaction as a template (protonate, add nucleophile, proton dance....) until the end when we can either lose a proton from nitrogen to form an imine or from a carbon to form an enamine. The deciding factor is the nature of the starting amine -- two hydrogens on the N will lead to an imine and only one hydrogen will lead to an enamine. We then saw how a special case of the imine reaction could be used to reduce a C=O to two separate C-H bonds (the Wolff-Kishner reaction).
At the end we broke up into groups for the first time and worked on acetal formation using a single equivalent of a diol rather than two equivalents of alcohol. An offer of a point and a half bonus on the exam led to an amazing display of hard work.
Getting Serious about C=O
Monday was a day to focus on the C=O bond. We started with where we left off on Friday: Using acid- or base-catalysis to make it easier to add water to a C=O and form a hydrate. We then took this up a step and changed the water to an alcohol -- same mechanism, same process, just with a carbon attached to the O when we are done, instead of an H. This works much better with acid catalysis and we mentioned how the equilibrium could be adjusted to go the way we want by adding or removing water. It was also mentioned that taking the reaction backwards (back to C=O) is something that you should be able to do.
I have posted Problem Set 5 and its key. Also, for those who are really working ahead, the Need to Know for Chapter 20 has been posted. See the links to the right.
Oh, and I was stunned that so few class members watched the season premiere of "The Amazing Race."
Exam Key Posted
I have posted the exam key in the list of links to the right. Links will also be found on the web site.....
The Start of Aldehydes and Ketones
We started Chapter 19 on Friday. A lot of what we talked about was review (how to make C=O from alcohols, how to add nucleophiles/electrophiles to a C=O bond, etc.). The major points to remember all came at the end: when adding nucleophiles to the C=O, it is easier to activate either the electrophile (the C=O) by protonation OR the nucleophile by deprotonation. This is a theme that we will see again and again, so it is worth your time right now to make sure that you have a good handle on the concept.
Problem set 4 and its key have been posted; links to the right in the normal space.
Exam #1, Over and Done With!
OK, we've all survived the first exam. I'm done grading only the first page and won't have it back until Monday, so you can sleep tonight without worrying about it. We'll start Chapter 19 tomorrow with the coverage expected to go like this: Friday: 19.1 - 19.5, Monday: 19.6 - 19.8, Wednesday: 19.9 - 19.11, Friday: 19.12, 14.
I'll post the Need to Know for Chapter 19 and next week's to-do list soon. Many of the links on the right will disappear as they are no longer current. They will, however, continue to be on the web page.
Also, Meagen is changing her tutoring for next week to Wednesday and Thursday....still 7 - 9 pm.
A few fun things
To help get you through the studying of the next few days, I've changed the chemistry video (this one is from GoogleVideo) and also the Wikimapia site of the week. This week's video features music from my daughter's favorite band (Relient K) with "Chapstick, Chapped Lips and Chemistry" and the map site is New Hampshire International Raceway, the scene of next Sunday's Nextel Cup race (to be won, hopefully, by Jeff Gordon).
Epoxides, epoxides, epoxides
Today was the last day for Chapter 18 and we talked about epoxides. Two main topics were covered: how to make them and how to open them. The syntheses were short (mcpba or halide+ water followed by base) but the reactions were a bit more complicated. Essentially it boils down to this -- if using acid to open up an epoxide, the nucleophile will attack a tertiary carbon. Otherwise, the nucleophile will attack the less hindered site. It is also important to consider the stereochemical (nucleophile on opposite side as O atom) consequences of the reactions.
Don't forget tomorrow's seminar at noon in Room 108. Sandwiches/beverages provided.
Ethers, an Introduction
Today we started Chapter 18 and the focus was on how to make ethers and what one can do with them after they are synthesized. Two main synthetic methods for ethers discussed were the Williamson ether synthesis and alkoxymercuration. For the Williamson, the key is the manufacture of the alkoxide followed the addition of an alkyl halide which can undergo an SN2 reaction with the alkoxide. The alkoxymercuration was shown to be an analogy to the hydroxymercuration that we covered in Chem 241.
There were two main reactions of ethers. First was the cleavage with HI -- this was the tricky one, as it required the determination of whether or not a tertiary carbon was attached to the oxygen before determining the ultimate fate of the ether. Basically: no tertiary carbon, the iodide attacks the less hindered carbon; with a tertiary carbon the protonated ether fragments to create a tertiary carbocation. We also discussed the Claisen rearrangement, and drew parallels to the Diels-Alder reaction.
I have corrected the second part of ps #2's
key (with some loss of resolution) and have posted
ps 3 and its
key. The
to-do list for next week is also up.
The end of Chapter 17
Today we finished the material in Chapter 17. There were a few main topics: The ability to control the nature of the stereocenter in substitution reactions by varying the nature of the reagents, oxidations of alcohols, and the use of protecting groups in synthesis. We also spent a little bit of time at the end discussing phenols and how they keep food from going rancid.
There was also general grumbling over Facebook's new "I know what you are doing and when" policy.
Our schedule for Chapter 18: Friday we will cover 18.1 - 18.6 and next Monday we will do 18.7 & 18.8.
As promised, here is last year's test (
page 1,
page 2,
page 3).
Tutoring Hours Changed for Tonight!
Meagen the tutor has informed me that she will be available for tutoring tonight from 6 - 8 pm instead of the normal time.
Reactions of Alcohols
Today was a day to learn about some of the reactions that alcohols undergo. We spent all of our time on two processes: Dehydration and halogenation. Some of it should have been review (examples of eliminations, etc.) but some of it (phosphorous oxychloride, thionyl chloride, etc.) were new ideas that probably will require some effort on your part to master. Luckily, the first part of
problem set two (and its
key) will help you with that. The second part of PS#2 covers material that we will discuss on Wednesday.
For those of you who are working ahead, I have also posted the Need to Know for
Chapter 18.
One week down, 13 to go
Today was a day to talk about the C=O system. At the beginning of class we looked at how molecular modeling indicates the polarization of the bond in terms of partial charges. We also saw that the LUMO corresponded closely the pi-system of the double bond and nearby C-H bonds. An analysis of the LUMO density showed that even though the LUMO took up a pretty big volume of space, any nucleophile would be most likely attracted to the C of the C=O.
We showed how these C=O systems can be converted into alcohols by treatment with a nucleophile, followed by protonation. In order to get "standard" alcohols, a hydrogen or carbon nucleophile must be used -- we looked at the examples of sodium borohydride, lithium aluminum hydride, and Grignard reagents. It is important to be able to draw the arrows for such reactions correctly; Problem Set #1 will give you practice at this.
I have posted the to-do list for the week of Sept 4 to the right.
