Rules of the Day 320N

1. A methyl ketone is the synthesis key recognition element (KRE) for synthesis by the acetoester synthesis.

2. The malonic ester synthesis is entirely analogous to the acetoester synthesis, except diethyl malonate is used and a substituted carboxylic acid derivative is the ultimate product following ester hydrolysis in acid (H3O+) and heating (loss of CO2).

3. A derivatized carboxylic acid function is the malonic ester synthesis key recognition element (KRE). These can be tough to spot so practice.

4. An enamine is formed when a secondary amine reacts with a ketone or aldehyde. The enamine can be thought of as the resonance hybrid of two contributing structures. The alpha-carbon atom is nucleophilic entirely analogous to an enolate.

5. Enamines can be alkylated by reaction with primary haloakanes, or acylated by reaction with acid chlorides. In these reactions you can think of enamines as slightly less reactive versions of enolates, yet enamines are made under relatively mild conditions (pH 4.0, no harsh base required).

6. The last step in an enamine reaction with either haloalkanes or acid chlorides involves opening the flask and adding water, mild acid and maybe some heat to remove the secondary amine and restore the original carbonyl group.

If you are having even a little trouble with mechanisms: Print out multiple copies of the new Mechanism Sheet 18 Microscopic Reversibility. Practice writing arrows and reagents in both directions (Acid catalyzed ester hydrolysis, starting at the top then working down and Fischer esterification, starting at the bottom then working up), taking advantage of the common structures drawn in red. Try to UNDERSTAND why each step occurs and why acid catalyzed ester hydrolysis uses water or H3O+ in several steps while Fischer Esterification used an alcohol or protonated alcohol. Do this several times until it makes sense. Then print out several copies of the Fischer esterification and acid catalyzed ester hydrolysis sheets and work them until it all makes sense. Keep asking yourself why each step occurs as it does (add a proton, make a bond etc.) until you understand why every step is the best choice. Compare your answers to the sheets you filled out in class.

If you are having even a little trouble with synthesis questions: You must know all the reactions, full stop. After you know your reactions very well, you need to learn the KRE's. The best way to learn these is to turn it into a game. Find some friends and get a list of all the reactions we have learned this semester. Each of you needs to write down an example of each reaction we have learned, with the product on a separate sheet of paper. For example, write an n-butyl Grignard reacting with 2-pentanone and put the product on a separate sheet. Make up examples of each reaction. Then give the product sheet to your friends and have them write down possible reactions that gave the products. There are often several ways to make the same product by the way. Do this for an hour and you will know your KRE's. When working synthesis problems, work backwards. Count carbons in products vs. reactants to identify where new C-C bonds are formed. When you know where the new C-C bonds are formed you can identify KRE's. Be systematic and you will get these.

Homework:

Read: Sections 19.6-19.7 in the ebook textbook. This text is part of the Longhorn Textbook access program.

Take the Daily Quiz 14 before 10 PM tomorrow. Click here to access the quiz.

Continue working on the Homework Problem Set 7, due at 10 PM on Monday, March 25. Click here to access the Homework Problem Set 7. Remember to do both the Aktiv learning and Gradescope portions of the homework! We will grade one problem for accuracy, and the rest for completeness.