Ch 22(18) Reactions at the alpha carbon of a carbonyl compounds

Question 1

A nucleophile can… to the what carbon

Answer 1

a nucleophile can add to the carbonyl carbon

Question 2

A…. can remove a proton from an alpha carbon

Answer 2

a base can remove a proton from an alpha carbon

(an alpha carbon is a carbon that is adjacent to a carbonyl carbon)

Question 3

What is the pKa of one of the hydrogens in CH₃CH₃

Answer 3

the pKa is greater than 60

Question 4

Hydrogens attacehd to sp³ carbons have very____pKa values

Answer 4

hydeogens attached to sp³ carbons have very high pKa values

Question 5

What is a carbon acid? What is the range of their pKa’s?

Answer 5

a compound that contains a relatively acidic hydrogen bonded to an sp³ carbon. The pKa’s range from 16~20 and 25

Question 6

The electrons left behind when a proton is removed from an alpha carbon are _____ onto the ____. Draw a picture

Answer 6

the electrons left behind when a proton is removed from an alpha carbon are delocalized onto an oxygen.

Question 7

Why are alpha carbons more acidic than other sp³ carbons

Answer 7

the electrons left behind when a proton is removed from an sp³ carbon are localized on the carbon.

The electrons left behind when a proton is removed from an alpha carbon are delocalized onto an oxygen.

deloocalization increases stability

(the more stable the base, the stronger its conjugate acid)

oxygen is better able to accommodate the electrons than carbon

Question 8

Why are protons on an alpha carbon of an aldehyde or ketone more acidic than a proton on an alpha carbon of an ester? What are their pKa’s? Draw a picture

Answer 8

esters are less acidic thal aldehydes and ketone because delocalization of the electrons left behind when the proton is removed has to compete with the delocalization of the lone pair onto the carbonyl oxygen

aldehydes and ketones 16-20

ester-25

Question 9

What happens when electrons can he delocalized onto two oxygens? Draw a picture.

Answer 9

The acidity of the alpha hydrogen increases

Question 10

How do tautomes differ? Draw a picture

Answer 10

tautomers differ in the location of the double bond and a hydrogen.

Question 11

For most ketones the ___ tautomer is more stable than the ___ tautomer. In what caseis the oppsite true.

Answer 11

For most ketones the keto tautomer is more stable than the enol tautomer. When the enol tautomer is aromatic it is more stable.

Question 12

What is the mech for a base catalyzed keto-enol interconversion? Draw it.

Answer 12

1. removal of a proton from the alpha carbon
2. protonnation on oxygen

Question 13

What is the mech for an acid catalyzed keto-enol interconversion? Draw it.

Answer 13

1. protionation on the oxygen
2. removal of a proton from the alpha carbon

Question 14

What happens when an alpha carbon is treated with a halogan and an acid catalyst?

Answer 14

one of the alpha carbons is replace by an halogen and HX is produced.

Question 15

What happen when an alpha carbon is treated with excess halogen and a base catalyst? Draw it.

Answer 15

all of the alpha hydrogens are replaced by the halogen and 2X^- is produced

Question 16

What happens when a carboxylic acid is treated with 1.PBr₃ (or P),Br. 2.H₂O

Answer 16

The HVZ reaction is used to replace the alpha carbon of a carboxylic acid with Br.

Question 17

What happen when the bromine of the alpha carbon of an aldehyde or ketone is treated with a waek base?

Answer 17

the Br is replaced by the weak base and Br is released as an ion.

Question 18

What happens when bromine of the alpha carbon of a carboxylic acid is treated with a weak or strong base?

Answer 18

The Br is replaced by the base.

Question 19

What can be used to form the enolate ion so the equilibrium lies to the right?

Answer 19

LDA can be use since DIA is produced in the reaction and it is a weaker acid then aldehydes and ketones.

Question 20

How is LDA synthesized ?

Answer 20

With diisopropylamine ,butyllithium and THF at -78ºC

Question 21

How do you alkylate the alpha carbon of ketones, esters and nitriles?

Answer 21

With 1. LDA/THF 2. alkyl halide with the desried alkyl group

Polyakylation will occur if a weak base (HO-) is used

Question 22

How do you snthesize an enamine?

Answer 22

When a ketone or aldehyde is treated with a secondary amine and trace acid an enamine and water are produced.

Question 23

How can you alkylate an alpha carbon via an enamine?

Answer 23

1. secondary amine,trace acid
2. akyl halide or acyl halide (eletrophile)(Sn2 Reaction)
3. HCl/H₂O

enamines react with electrophiles like enolates do

Question 24

alpha, beta-unsaturated aldehydes and ketones under go _______ and _____

Answer 24

alpha, beta unsaturated aldehydes and ketone undergo direct addation and conjugate?

-poor nucleophiles form the conjugate addation product

Question 25

Whan alpha beta unsaturated aldehyde or ketone is treated with a beta -diester what does the product look like and what are the reagents used?

Answer 25

the beta carbon of the alpha beta carbon is boned to the alpha carbon of the diester. An same ester ion must be used and along wih methol(same alkyl alchol)

Question 26

In the presence of catalytic acid or base, a ketone will exist in equilibrium with an \_\_\_

Answer 26

enol

Question 27

What are the factors that effect the equilibrium concentrations of an diketone and the enol

Answer 27

(1) The enol has a conjugated p system, which is a stabilizing factor , and (2) the enol can form an intramolecular H-bonding interaction between the hydroxyl proton and the nearby carbonyl group (shown with a gray dotted line above). Both of these factors serve to stabilize the enol.

Question 28

When treated with a strong base, the a position of a ketone is deprotonated to give a resonance-stabilized intermediate called an \_\_\_\_

Answer 28

enolate

Question 29

Enolates are ambident nucleophiles (ambi is Latin for “both” and dent is Latin for “teeth”), because they possess two nucleophilic sites, each of which can attack an electrophile. When the oxygen atom attacks an electrophile, it is called O-attack; and when the a carbon attacks an electrophile, it is called \_\_-attack.

Answer 29

C- attack C-attack is nevertheless more common than O-attack. All of the reactions presented in this chapter will be examples of C-attack. When drawing the mechanism of an enolate undergoing C-attack, it is technically more appropriate to draw the resonance structure of the enolate in which the negative charge appears on the oxygen atom

Question 30

Why are enolates more usful than enols

Answer 30

(1)enolates possess a full negative charge and are therefore more reactive than enols and (2) enolates can be isolated and stored for short periods of time, unlike enols, which cannot be isolated or stored. For these two reasons, the vast majority of reactions in this chapter proceed via enolate intermediates.

Question 31

What is an aldol

Answer 31

hydroxyl group is located specifically at the b position relative to the carbonyl group. The product of an aldol addition reaction is always a b-hydroxy aldehyde or ketone

Question 32

aldol addation mech

Answer 32

Question 33

Retro aldol reaction mech

Answer 33

Question 34

When heated in acidic or basic conditions, the product of an aldol addition reaction will undergo elimination to produce unsaturation between the alpha and _____ positions.

Answer 34

beta

Question 35

What is an aldol condensation

Answer 35

Question 36

mech for an aldol condensation

Answer 36

Question 37

Crossed aldol reactions

Answer 37

Question 38

Intermolecular aldol reactions

Answer 38

Compounds that possess two carbonyl groups can undergo intramolecular aldol reactions. Consider the reaction that occurs when 2,5-hexanedione is heated in the presence of aqueous sodium hydroxide.

Question 39

Claison condensation

Answer 39

Like aldehydes and ketones, esters also exhibit reversible condensation reactions.

Question 40

mech for claisen condensation

Answer 40

Question 41

A directed Claisen condensation can be performed in which LDA is used as a base to irreversibly form an ester enolate, which is then treated with a different ester.

Answer 41

Question 42

Claisen condensation

Answer 42

Question 43

under acidic conditions, ketones and aldehydes will undergo halogenation at the ____ position

Answer 43

alpha position this reaction is observed from chlorin, bromine and iodine

Question 44

Mech for acid catalyzed halogenations of ketones

Answer 44

with unsymmertical ketones bromination occurs primarily at the more substituted side of the ketone, the less substituted is observed as a minor product

Question 45

halogenated products can under go elimination when treated with a \_\_\_\_

Answer 45

base Li₂CO₃ pyridine tert-butoxide

Question 46

carboxyclic acids undergo alpha halogenation when treated with bromine in the presence of \_\_\_\_

Answer 46

PBr₃

Question 47

Hell-Volhard-Zelinsky reaction

Answer 47

Question 48

alpha halogenation in basic conditions

Answer 48

if more than one alpha hydrogen is present then it is difficult to achive monobromination

Question 49

haloform reaction mech

Answer 49

1)NaOH,Br₂/2)H₃O⁺ the reaction ust be followed bt a proton source

Question 50

x

Question 51

Dickmann cyclzation

Answer 51

1)NaOEt/2) H₃O⁺

Question 52

regionselective alkylation

Answer 52

Question 53

malonic ester synthesis trans forms a halide in to a \_\_\_\_\_

Answer 53

carboxylic acid with the introduction of two new carbon atoms

Question 54

acetoacetic ester synthesis is used to conert a alkyl halide into a \_\_\_\_\_\_.

Answer 54

methyl ketone with the introduction of three new carbons atoms