Rules of the Day
3-19-2024
Click here for a copy of the lectures notes I wrote in class
Click here for a copy of the handouts I used in class today
Featured Golden Rule of Chemistry: 10. A reaction mechanism describes the sequence of steps occurring during a reaction.10
1. It is important that you are able to write a balanced equation for each mechanism that we cover. To do this, keep track of all the atoms in all of the products produced during a reaction mechanism and balance that on the starting materials side of the equation. This will help you keep track of "acid or base catalyzed" vs. "acid or base promoted" as well as EQUIVALENTS. Doing this establishes a critical link between reaction mechanisms and how to use them properly in synthesis reactions!There are four new concepts associated with chapter 19. Click on these one at a time to get more information.
C) Beta-Dicarbonyl species are especially acidic
D) Conjugate addition to alpha,beta unsaturated carbonyl species.
2. A Claisen reaction is an "aldol with esters", also known as Dr. Evil meets an ester. At least 0.5 equivalents of the alkoxide corresponding to the alcohol portion of the ester is used to create an enolate that reacts with another molecule of ester via Mechanism B. For a movie of the Claisen reaction, click here. Claisen reactions are favorable (have a strong motive) because of the last deprotonation step. In the balanced overall Claisen reaction there are two molecules of starting ester required, one molecule of alkoxide base and two molecules of alcohol produced along with one product beta-ketoester.
3. A Dieckmann reaction is a cyclic version of the Claisen in which a diester reacts to give a 5 or 6-membered ring. Cyclic aldols are also possible. Number the C atoms for these!!
4. When there are several possible enolates in a molecule with two aldehydes/ketones, the product will be the most stable ring (5 or 6 membered ring).
5. When we balance a chemical reaction equation, we take account of all the molecules in the starting materials, reactants and products according to the mechanism. We generally only use whole numbers.
6. Equivalents are used to decide how to measure out the right amount of each reactant for a reaction, and we always designate that the key carbon containing starting material is present as 1.0 equivalents, and everything else scales accordingly, again based on the mechanism. When using a reaction in a synthesis we use equivalents.
7. The amount of base you add matters!! Only a catalytic amount of hydroxide is needed for an aldol to work, but at least 0.5 equivalents of alkoxide are needed for a Claisen to go to completion. Here we define 1.0 equivalents as the amount of the important carbon containing starting material used in the reaction. In the (noncyclic) Claisen, 0.5 equivalents of product are made, and according to the mechanism, the amount of base needed equals the amount of product made, ie.e 0.5 equivalents. For the same reason you need 1.0 equivalent of alkoxide for a Dieckmann to work (write out the overall balanced equation for the Dieckmann to see why this is true)!! This is confusing so check out the following two resources:
Click here to see a "Things you need to know" handout that explains "equivalents" in more detail.
8. The beta-ketoester Claisen products can be used for other cool reactions. The apha position of a beta ketoester can be easily deprotonated then alkylated in an SN2 reaction as long as sterics are not too much of a problem. In addition, Claisen products can undergo ester hydrolysis followed by heating to give decarboxylation and a ketone product.
9. The acetoester synthesis provides a simple way to make complex methyl ketones. The enolate is formed using 1.0 equivalent of strong base such as NaOEt, followed by 1) alkylation with a haloalkane, 2) acid catalyzed hydrolysis of the ester and heating (loss of CO2). The initial acetoacetate can actually be alkylated twice if sterics permit.
10. A methyl ketone is the synthesis key recognition element (KRE) for synthesis by the acetoacetate synthesis.
Here are some practice problems. You will not turn these in, but I have posted answers for you to check.
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 19.4-19.5 in the ebook textbook. This text is part of the Longhorn Textbook access program.
Take the Daily Quiz 13 before 10 PM tomorrow. Click here to access the quiz.
Start 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.
