Chapter 22 Flashcards
α-substitution:
Substitution of one of the _____ attached to the _____ carbon for an electrophile
H’s
α
α-substitution occurs via an _______ ion intermediate = a _____ that is adjacent to a C=O
enolate
C-
α-substitution can either occur via _______ or _______ mechanism
Nucleophilic addition
- acts as nuc
Nucleophilic acylation substitution
Carbonyl compounds with one or more _____-hydrogens rapidly interconvert with their corresponding enols. This represents a special type of isomerism known as _______
α
tautomerism
- acidic and basic
An H on the carbon α to a C=O is relatively _______
acidic
What is the pKa of an aldehyde/ketone?
20
What is the pKa of an ester?
24
What is the pKa of NaNH2?
38
What is the pKa of LDA?
40
What is the pKa of an NaH?
35
What is the pKa of a β-dicarbonyl aldehyde/ketone?
9
What is the pKa of an β-dicarbonyl monoester?
11
What is the pKa of an β-dicarbonyl diester?
13
What is the pKa of -OH?
15.7
What is the pKa of -OR?
16
What bases do you have to use if you want to deprotonate an aldehyde, ketone, or ester?
1) NaNH2
2) LDA
3) NaH
What bases can you use if you want to deprotonate β-dicarbonyl compounds
1) -OH
2) -OR
alkylation of enolate ions:
_____-groups can be added to the α position for some C=O
R
- doesn’t work with aldehydes or CA
For Sn2 reaction, R-X groups must be _______
1° or 2°
- mainly 1°
Enamines: weaker nucleophiles, so it must have ________ reactive starting materials
more
- methyl halide or resonance-stabilized halide
Enamines can be used as a _______ for ketones
protecting groups
- must come from 2° amine
In alpha-halogenation, the acidic mechanism is used to selectively replace _____ H with an X, but the basic mechanism is used for _______ additions
1 (acidic)
- up to 2
multiple (basic)
- always as much as possible
Acidic alpha-halogenation:
The halogen-substituted enol intermediate is _______ stable than the unsubstituted enol. This leads to each successive halogenation becoming _______
less
slower
- up to 2 halogen additions
Basic alpha-halogenation:
After the first X addition, the α H is more acidic because X = _______. Multiple additions result because _______ reactive product is formed
EWG
more
What reactants does the haloform reaction need?
1) methyl ketone
2) excess X2 (halogen gas)
3) excess base
The formation of iodoform via haloform reaction allows you to have qualitative tests that test for _______
methyl ketones
- turns yellow
The Hell-Volhard-Zelinsky (HVZ) reaction replaces an α-hydrogen of a _______ with a _______ atom
Carboxylic acid
Br
What are the reagents for the HVZ reaction?
1) Br2/PBr3
2) H2O
In aldol condensation, nucleophilic addition of an _______ ion to another carbonyl group
enolate
What are the 2 names for the product of an aldol condensation reaction?
1) aldol
2) β-hydroxyaldehyde
Dehydration of aldol products are done by adding _______ to the aldol product, which will cause water to be driven off to produce an _______ that is lower in energy
heat
α,β-unsaturated C=O
In dehydration of aldol products, the Hydroxide is usually not a good LG in E2 elimination, however it can be stabilized by the strong _______ step in which a negatively charged intermediate is stabilized
exothermic
Crossed/mixed aldol reactions are not desirable, except when one aldehyde has no _______ to grab
α-H
What are the 2 ways you can make a crossed/mixed aldol reaction better?
1) LDA to turn all of 1 reactant into nucleophile
2) an excess of electrophile
Intramoleclar aldol are often used to make _____, and _____ membered rings
5-
6-
The Claisen reaction combines 2 _______ molecules via nucleophilic acyl substitution
ester
In the Claisen reaction, moderate base must _______ the alkoxy group in the ester
match
What are the reagents for the Claisen reaction?
1) NaOR
2) H3O+
- H3O+ is needed because H on β-dicarbonyl are super acidic
The _______ reaction is basically an intermolecular Claisen reaction forming 5- or 6-membered rings
Dieckmann
Malonic ester: makes substituted derivatives of _______. This happens by alkylation or acylation on the carbon that is α to both C=O
acetic acids
- hydrolysis following claisen+alkylation reaction
_______ esters are similar to malonic ester, but the final product is a ketone
acetoacetic
- final product is ketone not acetic acid derivative
