Chapter 19: Enolate Anions and Enamines
Table of Contents:
Enols and Enolate Ions
Aldol Reaction
Aldol reaction is one of the most important reactions in this chapter and in semester 2 of organic chemistry. This reaction can occur under basic or acidic conditions.
Under Basic conditions
Under Acidic conditions
Mayya's Trick: How to predict the product of Aldol Condensation
Draw two molecules of the starting material and align =O of one with alpha carbon of the other
Get rid of =O and connect the carbon that had =O with the alpha carbon on another molecule through a double bond
There is also Crossed and Intramolecular Aldol Reactions. Crossed aldol is when instead of attacking itself, the enol or enolate attack another molecule of ketone or aldehyde. Intramolecular aldol is when one end of the molecule attacks another end of the molecule, forming a ring.
Mayya's Trick on how to predict reactants if the product of aldol condensation is given
Claisen and Diekmann Condensations
I think of Claisen condensation as a reaction that is similar to aldol condensation but with esters.
We will recognize Claisen reaction because we will see an ester as a reactant and -OR as the reagent where OR on the nucleophile is the same as OR group on the reactant.
The step in Claisen reaction where the base takes off a double alpha hydrogen is a very important step because this step drives the reaction in the forward direction.
Mayya's trick on predicting the product of Claisen Condensation
Dieckmann condensation refers to an intramolecular clause condensation where one part of the molecule attacks another part of the same molecule.
Crossed Claisen can also occur between two different esters.
How to predict reactants if the product of Claisen condensation is given
Hydrolysis and Decarboxylation of b-Ketoesters
Decarboxylation occurs where there is a carboxylic acid group (COOH) one carbon away from a carbonyl group (C=O). Under heat conditions, COOH leaves the molecule becoming carbon dioxide.
Beta keto ester can be converted into a carboxylic acid and undergo decarboxylation after with the aid of heat.
Alkylation Of Enamines
This reaction is useful in adding alkyl groups to the alpha carbon (carbon next to the C=O group) of an aldehyde or ketone.
First, a ketone or an aldehyde is converted into an enamine. An enamine can serve as a great tool to add alkyl groups to the alpha carbon. It can then be taken off to give ketone or aldehyde back.
Malonic Ester Synthesis
Malonic ester synthesis starts with a molecule called malonic ester. The product of malonic ester synthesis is a carboxylic acid with one or two alkyl groups added to the alpha carbon.
Let's try a synthesis example.
Acetoacetic Ester Synthesis
Acetoacetic ester synthesis is almost the same as malonic ester synthesis. The difference is that instead of malonic ester, it starts with an acetoacetic ester. The product of acetoacetic ester synthesis is methyl ketone with one or two alkyl groups on the alpha carbon.
Conjugate Addition to alpha,beta-Unsaturated Carbonyl Compounds
Alpha,beta -unsaturated carbonyl compounds are not only the products of Aldol condensation but can also serve as reactants in a reaction called Michael (also called 1,4 addition).
The nucleophiles are most often enolate anions, although other nucleophiles can add as well.
Decarboxylation can follow.
How to predict the product of Michael reaction
Mayya's Trick
Identify alpha beta unsaturated ketone or aldehyde (Molecule A) and label alpha and beta carbons
Identify alpha carbon on the other molecule (Molecule B)
Connect the alpha carbon of B to the beta carbon of A. Get rid of the alpha, beta double bond.
Let's take a look at different possible Michael nucleophiles and nucleophile acceptors.
Organocuprate or Gilman reagent adds R group to the beta carbon of Michael as well.
Grignard or Organolithium Reaction with Michael
Robinson Annulation
Robinson Annulation is two reactions combined. It is Michael reaction followed by intramolecular Aldol condensation.
Mayya's Trick
How to predict reactants when Robinson Annulation Product is Given
Identify double single double bond O
identify the alpha and beta carbons
break between alpha and beta and attach =O to the beta carbon
identify 1,5 =O and number the carbons 1 through 5
Break between carbon between carbons 3 and 4 and put a double bond between carbons 2 and 3 (if that doesn't work you might have to number carbons in the opposite direction)
Crossed Enolate Reactions Using LDA
LDA is a very strong base and a poor nucleophile. It is often used to generate enolate ions from carbonyl compounds such as ketones, aldehydes and esters. These enolate ions can further undergo aldol reaction.
Notes and Tricks
This chapter is considered one of the hardest chapters in the second semester of organic chemistry. It is often difficult for students to recognize which reaction they are dealing with or how to synthesize a certain compound. I have created some tricks to help you with this chapter!
Mayya's Trick
How To Recognize The Products Of Reactions In This Chapter
Mayya's Trick
How to predict reactants when Claisen product is given
Find alpha and beta carbons from the ester group
Break the bond between alpha and beta carbons
Attach OR (look at the base used) to the beta carbon
Mayya's Trick
How to predict reactants when Aldol product (α,β unsaturated carbonyl) is given
Identify alpha (next to C=O) and beta (next to alpha) carbons
break the bond between them
add =O to the beta carbon
How to predict reactants when Aldol product (β hydroxy ketone) is given
Identify alpha (next to C=O) and beta (next to alpha) carbons
break the bond between them
Turn OH on beta carbon into =O
Mayya's Trick
How to predict reactants when Michael product is given
Find 1,5 diketone
Number 1 through 5
Break between 2 and 3
Put double bond between 3 and 4
Finally, let's learn how to recognize what reactions we are dealing with in order to predict the products correctly.
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