Activity and enol structure of α-H
α-H activity
Factors that stabilize C- are conducive to "increasing acidity"
Too many hydrocarbon groups will "increase steric hindrance", which is not conducive to the attack of bases.
enol structure
LDA
Conditions of Use
LDA, THF, (low temperature)
preparation
CH3CH2CH2CH2Li HN（CHMe2)2→LDA
Selectivity
Preferential change to "polyhydrocarbyl substitution" (thermodynamics)
Remove the "strongly acidic" H (kinetics)
Select "Kinetic Products" only if you have a large volume of base.
Features
The reaction is "reversible"
Placed in D2O; intermediate energy displaces α-H
The final product will become a "racemic product"
Because the enol formula is a "planar structure"
alpha halogenation reaction
aldehydes and ketones
Catalytic mechanism
Removal of H is the rate-determining step of the reaction
base
Can be three substituted, finally becoming "carboxylic acid" and "haloform"
The iodoform reaction is the easiest to carry out
"Protect the carbonyl group" when eliminating α-haloketones
Because bases are also nucleophiles and will attack the carbonyl carbon atom
carboxylic acid
mechanism
1. First turn into acid halide
3. React with carboxylic acid, two Br for each person
alpha halocarboxylic acid
4. The acid halide can continue to react and become an α-halogenated acid halide.
αhalogenated acid halide Zn→ketene
alpha alkylation reaction
product
Introduce "alkyl" at α position
via enol anion
condition
Base (LDA or NaNH2) THF RX
via imine or enamine
imine
mechanism
1. First generate C and N double bonds
2. Pull out α-H to generate C-, and perform enol-like interconversion
4. Remove the imine from the acid and change it back to the carbonyl group
enamine
mechanism
1. First form C and N single bonds, then pull α-H (more acidic) into C=C
Features
The yield can be increased by refluxing and heating
beta dicarbonyl compounds
condition
1.Alkali (NaOH or EtONa), H2O
Features
Its α-H is very reactive and can be easily removed by alkaline reagents
Aldol condensation
product
Generate β-hydroxyaldehyde → (easy to form by adding acid) α,β-unsaturated ketone
α,β-unsaturated ketones can participate in "Michael addition"
mechanism
2. Attack the carbonyl carbon
3. In acidity, hydroxyl and α-H are eliminated (no acid is eliminated)
Features
If a five- or six-membered ring can be formed, intramolecular aldol condensation can be formed
Different aldehyde and ketone reactions have different and mixed products.
If one of the parties has no α-H, a simpler product can be generated
acylation reaction
Claisen condensation
product
Introduction of "acyl" or "aldehyde group" at the α position of ester or ketone (reaction with formate)
Preparation of beta dicarbonyl compounds
mechanism
1. Pull out α-H to form C-
4. Enol-type mechanisms may be formed
Features
Use equal or excess amounts of alkali
An ester with two α-Hs is required for the reaction to proceed efficiently
Only an α-H ester requires a stronger base to react
The reaction is reversible, from an acyl ester to two esters in a small amount of base and an equal amount of alcohol.
condition
"Ester-to-ester" or "ketone-to-ester" reaction
Dieckmann condensation
If a five- or six-membered ring can be formed, intramolecular condensation can be formed
Products with α-H are preferentially formed
Michael reaction and Robinson reaction
Michael's reaction
condition
Reaction of nucleophiles with α,β-unsaturated ketones
It can also be other unsaturated aldehydes, esters, nitro groups, etc.
Base (EtONa, EtOH or others)
product
The double bond disappears and β-C is connected to the nucleophile
When synthesizing, if the connecting group has a double bond, first consider whether there can be a conjugated double bond.
Robinson reaction
After MIchael, if there is a suitable α-H, it can be dehydrated to form a ring
decarboxylation reaction
dilute base
Decarboxylation to ketones with CO2
Concentrated alkali
Decarboxylation to ester, equivalent to reverse Claisen condensation
Other condensation reactions
Mannich reaction
condition
R-CHO NHMe2 R'-CH2COR" under H
mechanism
1.R-CHO reacts with NHMe2 to form R-CH=N Me2
2.R'-CH2COR" enol interconversion, double bond attacks the C of R-CH=N Me2
3. Remove proton and become carbonyl group
benzoin condensation
mechanism
2. Polarity reversal, H on carbonyl group C migrates to O, O- becomes C-
3.C-attacks another carbonyl carbon
4.H migration on O, CN- is removed to form a carbonyl group
condition
Reactions between aromatic aldehydes without α-H
Catalyst CN- or other catalysts such as vitamin B1
Generation of heterocyclic compounds
H2NOH and dicarbonyl compounds can be converted into pyridine in one step
Hantzsch synthesis of pyridine rings
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