Alpha Substitution of Carbonyl Compounds

What is an alpha hydrogen?

Bonded to an Alpha Carbon.

They are relativley ACIDIC (cuz of delocalization)

Alpha hydrogen general reaction

Enolate

Has the one with the major contribution is the one on the bottom right there (- on the oxygen)

• BUT generally it is easier to remember that the Carbon is on the negative charge there.

GENERALLY, enolates go out and attack things

bases i mean

Carbonyl Compounds with enols (acidic reaction)

As you can see, if we add an acid, instead you get a enol. (alkene and alcohol)

Enols can also attack things

Which generally does the same thing as enolates.

Enolates vs Enols as attackers (nucleophiles)

Enolates are better since they have a negative charge.

Carbonyl Compounds with alpha hydrogens convert between their keto and enol forms.

KETO FORM IS HEAVILY FAVORED.

Asymmetric Molecules with many alpha hydrogens. (which one gets deprotonated?)

MOST SUBSTITUED gets deprotonated.

What happens if you want to deprotenate the non-substituted alpha hydrogen?

We use LDA

• LDA is sooo large, that it removes the alpha hydrogen.

What happens IRL with bases in alpha substitution

you just keep going at those alpha carbons

LDA and it’s relationship to alpha hydrogens.

It only removes one and adds one thing.

Halogenation of an Alpha Carbon (BASIC)

BASIC CONDITIONS

Mech of alpha halogenation (basic)

Halogenation of an Alpha Carbon (ACIDIC)

ONLY ONE GETS REMOVES

Acid can be TFA.

Halogenated Alpha Carbons (ACIDIC mechanism)

Can a ketone be converted to a carboxylic acid

Not with an OH-

Converting a ketone to a carboxylic acid

HALOFORM REACTION

MUST be a methyl ketone

Haloform Reaction mechanism (why is it important)

Carbon is given a ton of halogens to it becomes a good leaving group.

HCCL3 can be used to determine if you have a methyl ketone since HCCl3 (chloroform) is insoluble in water.

OR

HCI3 (which becomes a precipitate.)

It helps see if we have a methyl ketone

Aldol Condensation.

SUPER IMPORTANT HOLY SHEEE

1. OH-

2. H2O

Aldol Condensation mechanism.

(you can ignore that last step if you want)

Aldol Reaction SHorcut.

Time stamp: 3:21

Video 3

Also called an aldol

Aldehyde + Alcohol

Claisen reaction

Involves esters instead of aldehydes or ketones.

1. RO-

2. H+ Quench

RO- group MUST be the same as the ester

Nonmatching Claisen,.

THIS IS NOT A CLAISEN REACTION

• THis is what happens when they do not match.

Claisen Reaction Mech

We kick out the new esters ester group.

Chris’s Shortcut for a Claisen

Beta Decarboxylation

Beta Keto Ester

HO-

Beta Decarboxylation

Beta Keto carboxylate

just heat

Beta Decarboxylation mechanism

What the heck

Beta Keto Compounds

Molecules that have two C = O groups.

One at the Beta carbon. This makes alpha hydrogens even more acidic due to greater resonance.

IT IS VERY STABLE.

Beta Keto Compounds can reach out and react with things

Acetoacetic Ester Synthesis

1 RO-

2. R1Br

3. RO-

4. R2Br

5. H3O+, Heat

Acetoacetic Ester Synthesis mechanisms

You get a side product of CO2

Acetoacetic Ester Synthesis mechanisms

You get a side product of CO2

You can replace steps 3 and 4 to only get the removal of one H

Malonic Ester Synthesis

Very similar to Acetoacetic ester synthesis.

Acidity Trends

LDA by itself