19.6: Basicity Of Aldehydes & Ketones

Front 1

Aldehydes & ketones in solution are considerably __ basic than alcohols

Back 1

less (conjugate acids are more acidic because of solvent effect: in gas phase, aldehydes & ketones more basic, in solution, solvation of protonated alcohol by hydrogen bonding is evidently so effective that it outweighs resonance stabilization of protonated aldehyde/ketone

Front 2

Addition

Back 2

Front 3

In all carbonyl-addition reactions, the more electropositive species adds to

Back 3

the carbonyl oxygen, & the more electronegative species adds to the carbonyl carbon

Front 4

Nucleophilic carbonyl addition

Back 4

Reaction of a nucleophile @ carbonyl carbon: i.e. cyanide ion donates e to carbonyl C of ald/ket & carbonyl o accepts displaced e pair & assumes neg charge, which is protonated by h2o or hcn

Front 5

Nucleophilic carbonyl addition occurs even though the C-O bond is stronger than the C-C pi bond because

Back 5

the unshared e pair & neg charge formed in the mech is transferred to the electroneg O & same rxn of alkene would place unshared pair & neg charge on C

Front 6

Can a nucleophile add to the carbonyl oxygen?

Back 6

No: nucs always react w carbonyl groups @ the carbonyl C

Front 7

How does the carbonyl carbon change hybridization when attacked?

Back 7

sp2 to sp3, trigonal planar to tetrahedral: angle compresses, groups bound to the carbonyl become closer together

Front 8

Why does the addition geometry occur?

Back 8

The bonding pi MO of the carbonyl group is fully occupied w 2 e and cannot have any more so e pair of nuc interacts w LUMO: antibonding MO w lobes above & below & the nuc must begin bonding w carbonyl from direction along which lUMO is conc

Front 9

When the antibondnig pi* MO is filled

Back 9

the C=O bond is weakened and breaks

Front 10

Second mechanism for carbonyl addition

Back 10

analogous to mech for addition of acids to alkenes: protonation of carbonyl O

Front 11

Mechanism 2.2 carbonyl addition

Back 11

Loss of a proton to solvent (weak base H2O can react because protonated O makes a strong Lewis acid)

Front 12

Does hydration of aldehydes & ketones occur in neutral & basic solutions?

Back 12

Yes

Front 13

Mechanism 2.2 direction of approach

Back 13

above or below bc of shape of LUMO

Front 14

Hydration & cyanohydrin formation are both __

Back 14

reversible rxns

Front 15

Whether the equilibrium favors addition product or carbonyl cmpd depends on

Back 15

the structure of the carbonyl cmpd

Front 16

Addition is more favorable for aldehydes or ketones?

Back 16

Aldehydes

Front 17

Electronegative groups near the carbonyl C make addition ___ favorable

Back 17

more

Front 18

Groups that donate e by resonance to the carbonyl C make addition ___ favorable

Back 18

less

Front 19

The equilibria for all addition rxns show similar effects of structure important bc

Back 19

the reactivities of carbonyl cmpds follow similar trends

Front 20

Reason for the effect of structure on carbonyl addition?

Back 20

The relative stabilities of the carbonyl compound & the addition product govern delta G for addition: the primary effect on the hydration equilibrium is the difference in the stabilities of the carbonyl compounds - Added stability in the carbonyl cmpd inc delta G & dec equilibrium constant for formation of an addition product

Front 21

Carbonyl cmpds are stabilized bc

Back 21

one resonance structure reflects polarity of carbonyl group w characteristics of a carbocation so anything that stabilizes carbocations also stabilizes carbonyl cmpds

Front 22

Why are ketones more stable than aldehydes?

Back 22

Alkyl groups stabilize carbocations, so the equilibria for additions are less favorable

Front 23

Formaldehyde has 2 hydrogens so its equilibrium constant for hydration is

Back 23

large

Front 24

Electronegative groups such as halogens ___ carbocations

Back 24

destabilize by polar effect & carbonyl cmpds, so make equilibria for addition more favorable

Front 25

Groups that are conjugated w the carbonyl group such as phenyl of benzaldehyde

Back 25

stabilize carbocations by resonance & hence stabilize carbonyl cmpds: cannot occur in hydrate bc carbonyl no longer present

Front 26

Aryl aldehydes & ketones have ___ hydration equilibria

Back 26

relatively unfavorable

Front 27

Steric effect of carbonyl addition

Back 27

As size of groups bound to carbonyl carbon inc, VDW in addition cmpds inc in importance

Front 28

Cmpds w favorable addition equilibria tend to react

Back 28

most rapidly in addition rxns

Front 29

Aldehydes are generally ___ than ketones in addition rxns

Back 29

more reactive

Front 30

Formaldehyde is ___ reactive than many other simple aldehydes

Back 30

more

Front 31

Reason for parallel trends in rates and equilibria

Back 31

Transition states for addition rxns resemble addition products

Front 32

LiAlH4 is a source of

Back 32

a hydride ion (very basic) & bc H is more electroneg than Al, the Al-H bonds of the -AlH3 ion carry a substantial fraction of the neg charge

Front 33

LiAlH4 must be used in __ solvents

Back 33

dry, such as anhydrous ether and THF

Front 34

The rxn of LiAlH4 w aldehydes & ketones involves nuc rxn of hydride @ __ and the lithium ion acts as a ___ by ___

Back 34

carbonyl C - Lewis acid catalyst by coordinating to the carbonyl oxygen

Front 35

The addition product (an alkoxide salt) can react w AlH3 & resulting product can serve as

Back 35

a source of hydride: similar process at each stage of reduction until all hydrides consumed

Front 36

After the reduction is complete, the alcohol prod exists as

Back 36

an alkoxide addition cmpd w aluminum, converted separately into alcohol (proton from HCl or aq. NH4Cl)

Front 37

Sodium ion is a __ LA than lithium ion

Back 37

weaker, so NaBH4 reductions carried out in protic solvents such as alcohols

Front 38

Hydrogen bonding btwn alcohol solvent & carbonyl group serves as

Back 38

weak acid catalysis that activates the carbonyl group

Front 39

Are all four hydride equivalents of NaBH4 active in reduction?

Back 39

Yes

Front 40

Back 40

Front 41

The net effect of the Grignard reaction followed by protonolysis is

Back 41

addition of R-H (R=alkyl or aryl group) across the C=O double bond

Front 42

When an aldehyde or ketone reacts w a large excess of an alcohol in the presence of a trace of strong acid

Back 42

an acetal is formed

Front 43

Back 43

Front 44

acetal

Back 44

cmpd in which 2 ether O are bound to same C (ethers of carbonyl hydrates, or gem-diols)

Front 45

How many equivalents of alcohol are consumed in each acetal-forming reaction?

Back 45

2

Front 46

One equivalent of a 1,2 or 1,3-diol can react to form a

Back 46

cyclic acetal in which the acetal group is part of a 5 or 6 membered ring, respectively

Front 47

Back 47

Front 48

Is the formation of acetals reversible?

Back 48

Yes

Front 49

The reaction is driven to the right by

Back 49

the use of excess alcohol as the solvent or the removal of the water by-product, or both

Front 50

benzene-water azeotrope

Back 50

mixture of benzene and water that has a lower boiling point than either benzene or water alone

Front 51

Mechanism for acetal formation

Back 51

acid-catalyzed addition of the alcohol to the carbonyl group to give a hemiacetal, which reacts when OH is protonated & water lost to give relatively stable carbocation, an a-alkoxy carbocation

Front 52

hemiacetal

Back 52

compound with an OR and OH group on same carbon

Front 53

Mechanism 2

Back 53

Loss of water from the hemiacetal is an Sn1 rxn -> nuc rxn of an alcohol w the cation & deprotonation of nuc O

Front 54

Mechanism for acetal formation is really combination of

Back 54

acid-catalyzed carbonyl addition followed by substitution by SN1 mechanism

Front 55

Acetal hydrolysis

Back 55

acetals in presence of acid & excess h2o transformed rapidly back into corresponding carbonyl cmpds & alcohols

Front 56

The formation of hemiacetals is catalyzed by

Back 56

acids and bases

Front 57

the conversion of hemiacetals into acetals is catalyzed

Back 57

only by acids

Front 58

In what solutions are acetals stable?

Back 58

basic and neutral

Front 59

Hemiacetals in most cases cannot be isolated because

Back 59

they react further to yield acetals (in alcohol solution under acidic conditions) or decompose to aldehydes or ketones and an alcohol

Front 60

Do simple aldehydes form appreciable amts of hemiacetals in alcohol solution?

Back 60

Yes, just as they form appreciable amounts of hydrates in H2O

Front 61

hydroxy aldehydes spontaneously form

Back 61

five and six membered cyclic hemiacetals, and most are stable cmpds that can be isolated

Front 62

Intramolecular rxns are faster and..

Back 62

favored thermodynamically (have larger equilibrium constants)

Front 63

Protecting group

Back 63

chemical disguise so that a reagent reacts w one mlc and not another: most common are acetals for aldehydes & ketones

Front 64

Acetals are commonly used to protect the carbonyl groups of aldehydes & ketones from

Back 64

basic, nuc reagents

Front 65

Once the protection is no longer needed

Back 65

The acetal protecting group is removed, carbonyl re-exposed by treatment w dilute aq. acid

Front 66

Primary amine

Back 66

organic derivative of ammonia in which only one ammonia hydrogen replaced by an alkyl or aryl group

Front 67

imine

Back 67

nitrogen analog of an aldehyde or ketone in which C=O group replaced by C=NR group

Front 68

Back 68

reversible, generally w acid or base catalysis or w heat, typically driven to completion by ppt of imine removal of H2O or both

Front 69

Mechanism imine formation

Back 69

nuc addition to carbonyl to give unstable carbinolamine

Front 70

carbinolamine

Back 70

cmpd w amine group -NH2, -NHR or NR2 & hydroxy group on same C

Front 71

Mechanism imine formation 2

Back 71

carbinolamine undergoes acid-catalyzed dehydration to form imines, faster than dehydration of ordinary alcohol

Front 72

Why is imine formation catalyzed by acids?

Back 72

The dehydration is typically the rate-limiting step, but if acid conc is too high --> the protonated (pulls equilibrium to left) amine (basic) cannot act as a nuc

Front 73

Uses of imines

Back 73

preparation of amines, characterization of aldehydes & ketones

Front 74

derivatives

Back 74

crystalline cmpds: basis for ID of cmpd when isolated from a source or from a diff. rxn

Front 75

Why is it important to prepare derivatives?

Back 75

If two compounds have very similar mp or bp

Front 76

secondary amine

Back 76

R2NH

Front 77

Enamine

Back 77

amine nitrogen bound to a carbon that is part of a db

Front 78

provided that the carbonyl has an a-hydrogen, formation of a ___ occurs when a secondary amine reacts with an aldehyde or ketone

Back 78

Front 79

Is this process reversible?

Back 79

Yes (formation of an enamine) & must be driven to completion by the removal of one of reaction products (usually H2O)

Front 80

In what do enamines revert to the corresponding carbonyl cmpds?

Back 80

aqueous acid

Front 81

Mechanism of enamine formation

Back 81

Nuc addition: carbinolamine w no hydrogen on nitrogen so imine formation cannot occur

Front 82

Enamine mech 2

Back 82

dehydration of carbinolamine: loss of H from an adjacent C

Front 83

Why don't primary amines react w aldehydes or ketones to form enamines rather than imines?

Back 83

The enamines bear the same relationship to imines that enols bear to ketones

Front 84

What is more stable, an imine or enamine?

Back 84

Imine

Front 85

tertiary amine

Back 85

R3N

Front 86

Do tertiary amines react w aldehydes or ketones to form stable derivatives?

Back 86

no

Front 87

Tertiary amines are good nuc but have no ____ so cannot form carbinolamines

Back 87

NH hydrogens - adducts w aldehydes & ketones are unstable, can only break down to starting materials