Chapter 22

Question 1

α-substitution:
Substitution of one of the _____ attached to the _____ carbon for an electrophile

Answer 1

H’s
α

Question 2

α-substitution occurs via an _______ ion intermediate = a _____ that is adjacent to a C=O

Answer 2

enolate
C-

Question 3

α-substitution can either occur via _______ or _______ mechanism

Answer 3

Nucleophilic addition
- acts as nuc
Nucleophilic acylation substitution

Question 4

Carbonyl compounds with one or more _____-hydrogens rapidly interconvert with their corresponding enols. This represents a special type of isomerism known as _______

Answer 4

α
tautomerism
- acidic and basic

Question 5

An H on the carbon α to a C=O is relatively _______

Answer 5

acidic

Question 6

What is the pKa of an aldehyde/ketone?

Answer 6

20

Question 7

What is the pKa of an ester?

Answer 7

24

Question 8

What is the pKa of NaNH2?

Answer 8

38

Question 9

What is the pKa of LDA?

Answer 9

40

Question 10

What is the pKa of an NaH?

Answer 10

35

Question 11

What is the pKa of a β-dicarbonyl aldehyde/ketone?

Answer 11

9

Question 12

What is the pKa of an β-dicarbonyl monoester?

Answer 12

11

Question 13

What is the pKa of an β-dicarbonyl diester?

Answer 13

13

Question 14

What is the pKa of -OH?

Answer 14

15.7

Question 15

What is the pKa of -OR?

Answer 15

16

Question 16

What bases do you have to use if you want to deprotonate an aldehyde, ketone, or ester?

Answer 16

1) NaNH2
2) LDA
3) NaH

Question 17

What bases can you use if you want to deprotonate β-dicarbonyl compounds

Answer 17

1) -OH
2) -OR

Question 18

alkylation of enolate ions:
_____-groups can be added to the α position for some C=O

Answer 18

R
- doesn’t work with aldehydes or CA

Question 19

For Sn2 reaction, R-X groups must be _______

Answer 19

methyl, 1° or 2°
- mainly methyl or 1°

Question 20

Enamines: weaker nucleophiles, so it must have ________ reactive starting materials

Answer 20

more
- methyl halide or resonance-stabilized halide

Question 21

Enamines can be used as a _______ for ketones

Answer 21

protecting groups
- must come from 2° amine
- to prevent O-alkylation

Question 22

In alpha-halogenation, the acidic mechanism is used to selectively replace _____ H with an X, but the basic mechanism is used for _______ additions

Answer 22

1 (acidic)
- up to 2
multiple (basic)
- always as much as possible

Question 23

Acidic alpha-halogenation:
The halogen-substituted enol intermediate is _______ stable than the unsubstituted enol. This leads to each successive halogenation becoming _______

Answer 23

less
slower
- up to 2 halogen additions

Question 24

Basic alpha-halogenation:
After the first X addition, the α H is more acidic because X = _______. Multiple additions result because _______ reactive product is formed

Answer 24

EWG
more

Question 25

What reactants does the haloform reaction need?

Answer 25

1) methyl ketone 2) excess X2 (halogen gas) 3) excess base

Question 26

The formation of iodoform via haloform reaction allows you to have qualitative tests that test for _______

Answer 26

methyl ketones - turns yellow

Question 27

The Hell-Volhard-Zelinsky (HVZ) reaction replaces an α-hydrogen of a _______ with a _______ atom

Answer 27

Carboxylic acid Br

Question 28

What are the reagents for the HVZ reaction?

Answer 28

1) Br2/PBr3 2) H2O

Question 29

In aldol condensation, nucleophilic addition of an _______ ion to another carbonyl group

Answer 29

enolate

Question 30

What are the 2 names for the product of an aldol condensation reaction?

Answer 30

1) aldol 2) β-hydroxyaldehyde

Question 31

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

Answer 31

heat α,β-unsaturated C=O

Question 32

What reagents are needed for aldol condensation with dehydration?

Answer 32

NaOH heat

Question 33

In dehydration of aldol products, the _______ 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

Answer 33

Hydroxide exothermic

Question 34

Crossed/mixed aldol reactions are not desirable (feasible), except when one aldehyde has no _______ to grab

Answer 34

α-H

Question 35

What are the 2 ways you can make a crossed/mixed aldol reaction better?

Answer 35

1) LDA to turn all of 1 reactant into nucleophile 2) an excess of electrophile

Question 36

Intramoleclar aldol are often used to make _____, and _____ membered rings

Answer 36

5- 6-

Question 37

The Claisen reaction combines 2 _______ molecules via nucleophilic acyl substitution

Answer 37

ester

Question 38

In the Claisen reaction, moderate base must _______ the alkoxy group in the ester

Answer 38

match

Question 39

What are the reagents for the Claisen reaction?

Answer 39

1) NaOR 2) H3O+ - H3O+ is needed because H on β-dicarbonyl are super acidic - NaOR must match the ester OR

Question 40

The _______ reaction is basically an intermolecular Claisen reaction forming 5- or 6-membered rings

Answer 40

Dieckmann Condensation

Question 41

Malonic ester: makes substituted derivatives of _______. This happens by alkylation or acylation on the carbon that is α to both C=O

Answer 41

acetic acids - hydrolysis following claisen+alkylation reaction

Question 42

_______ esters are similar to malonic ester, but the final product is a ketone

Answer 42

acetoacetic - final product is ketone not acetic acid derivative

Question 43

the Michael reaction works with _______ reactive nucleophiles that attack the _______ position in a α,β-unsaturated carbonyl

Answer 43

less β - Aka 1,4 addition and conjugate addition

Question 44

Conjugate addition of a _______ (Michael _______) to the double bond of a α,β-unsaturated carbonyl compound (Michael _______) is called a Michael addition

Answer 44

carbanion donor acceptor

Question 45

What are some examples of Michael donors?

Answer 45

1) -CN 2) R2CuLi 3) enamine 4) enolate 5) amine 6) Michael (deprotonated β-dicarbonyl)

Question 46

Michael + Aldol reaction = _______

Answer 46

Robinson annulation

Question 47

What are the reagents for Robinson annulation?

Answer 47

α,β-unsaturated C=O NaOH heat