14-alpha substitution reactions of carbonyls

alpha substitution reactions

enolate (carbon - charge) binds to stuff

enol (C=C) binds to stuff

enolate

are better nucleophiles since they have negative charges

enol

keto-enol tautomerization

-reaction at equilibrium

-NOT a resonance

tautomers are defined

as constitutional isomers that interconvert at rapid equilibrium

although this inter convention occurs constantly

the keto form is favored

how to deprotonate alpha hydrogens

typical base (OH-) or LDA

Typical base (OH-) deprotonates

alpha hydrogens that are more substituted

multiple products form

LDA deprotonates

alpha hydrogen that are less substituted

forms one product

Base promoted alpha halogenations

all alpha hydrogens get replaced by halogen

1. OH-

2. Br2 (Xs)

Acid Catalyzed alpha Halogenation

only one alpha hydrogen is replaced with halogen

1. Acid (TFA)

2. X2

Alpha Deuteration

Replacement of all alpha hydrogen with deuterium (d).

1. acid or base.

2. D2O

Haloform reaction ( need CH3)

Complete halogenation of a methyl ketone in basic conditions.

1) OH-, (Xs) X2

haloform reaction produces

a carboxylate and HCX3

HCX3 is a yellow precipitate, useful lab test

Aldol condensation

aldehyde + aldehyde

-ketone + ketone

-or aldehyde reacts with a ketone

reagent (OH-, H2O)

aldol condensation reaction mechanism

OH - takes a H from the alpha carbon

the carbanion adds to the carbonly carbon of an aldehyde or ketone

initial product is a

beta hydroxy aldehyde or ketone

plus acid and heat

a, b, unsaturated aldehyde/ ketone

Claisen Condensation Reaction

- the aldol reaction with an ester.

- deprotonation of the α-C of an ester and the addition of the anion to the carbonyl carbon of a second ester.

- forms a β-ketoester

- has a biological application in fatty acid synthesis

Beta -decarboxylation

B-keto esters are converted to the original ester reactants

add OH- ( deprotonates OR group)

Add heat and forces CO2 group to leave

quench (H2O)

get your original reactant

Acetoacetic Ester Synthesis reagents

1. NaOEt

2. R-X

3. NaOEt

4. R-X

5. H3O+, ∆

OEt-, or OR- must be matching (reagents and on the ester)

product from acetoacetic ester synthesis

methyl ketone with 2 & 4 attached at alpha carbon

+CO2

undergoes beta decarboxylation

Malonic Ester synthesis (reagents)

1. NaOEt

2. R-X

3. NaOEt

4. R-X

5. H3O+, ∆

Malonic Ester Synthesis products

carboxylic acid