University:
Amherst College
Course:
CHEM 221 | Organic Chemistry I
Academic year:

2022
Views:

333

Pages:

3
Author:

Chandler Lewis

Lecture outline Here's an interesting feature of esters that have a carbonyl group in the β-position. When they're hydrolyzed to carboxylic acids, the acids lose CO2 very easily. O O C C C O C OEt O O C C C OH CH Q: That is sooooo cool. Please explain how that happens. A: [sigh…] if you insist… The mechanism is the key. The carbonyl must be there, and it must be in the right place (note the 6-membered ring transition state.) Plus, the thing that can lose CO2 is a carboxylic acid, not an ester. If you can write the mechanism above , you already know all of this, and there's nothing more to learn (i.e. memorize). Now, why is this important? In practice, direct alkylations of simple carbonyl compounds are often difficult and messy. The deprotonation step requires a super strong base, and low-temp, water-free, inert atmosphere conditions. Plus, the reactions can be hard to control, and the alkylated product and enolate sometimes get together in the reaction mixture and decide to swap a proton when you're not looking. That makes unwanted byproducts like dialkylated material. Consider, for example, mono- and di-alkylation of acetone shown below — How would we carry out each of these steps via a direct alkylation method? CH3 O O C C CH3 CH3 O R CH2 CH3 C R CH R' Now, how much easier is this? O CH3 C O CO2Et CH2 CH3 C O CO2Et CH C CH3 R CO2Et C R R' and then, just hydrolyze and decarboxylate, and voila! You've just learned the "acetoacetic ester synthesis" — this is just an easy way to make a substituted acetone derivative. If one carries out the same sequence of reactions starting with a "double ester", hydrolysis and decarboxylation produces a substituted acetic acid derivative — that's the "malonic ester synthesis". So that we don't depart completely from our nice reaction numbering scheme, let's call these reactions 6 and 7. How would you make the compounds below starting from either diethyl malonate (EtOCO–CH2–COOEt) or ethyl acetoacetate (CH3CO–CH2–COOEt)? Ph O CO2H Here are some more interesting targets — same choice of starting materials (isn't it great to have a choice?) Ph OH CO2Et

Lecture Outline April 9

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