Organic Chemistry - Nucleophilc Add (Aldehyde + Ketone)

Front 1

What are common aldehydes and ketones?

Back 1

Aldehydes:
living organisms - Pyridoxal phosphate (PLP) as coenzyme
-industry - formaldehyde insulates materials and resins

Ketones:
Living organisms - Hydrocortisone is a steroid hormone secreted by adrenal glands
Industry - Acetone used as industrial solvent

Front 2

How are aldehydes formed?

Back 2

Carboxylic esters reduce to aldehydes using diisobuylaluminum hydride (DIBAH) and toluene

Oxidation of primary alcohols using PCC, CH2Cl2

Front 3

How are ketones formed?

Back 3

Secondary alcohols oxidized by PCC, CH2Cl2

Aryl Ketones from Friedel Craft acylations AlCl3 + acetyl chloride

Front 4

What are properties in oxidation of aldehydes and ketones?

Back 4

aldehydes:
-easily oxidized to carboxylic acids
-common oxidizing agent = CrO3
-sometimes KMnO4 and hot HNO3
-proceed through intermediate 1,1 diols called hydrates

Ketones:
-inert towards oxidation

Front 5

What are characteristics of nucleophilic addition reactions of aldehydes and ketones?

Back 5

Nu approaches C=O at a 75 degree angle

carbonyl rehybridizes to sp3

tetrahedral alkoxide ion intermediate, can eliminate H20 to give C=Nu or protonate to form stable alcohol

aldehydes more reactive than ketones because less sterically hindered, C=O of aldehyde more polarized

Front 6

What happens in Nucleophilic addition of H20 to aldehydes and ketones?

Back 6

hydration reaction

both give 1,1 diols or geminal (gem) diols (exception is formaldehyde)

catalyzed by both acid and base

base mechanism:
-hydroxide is good nucleophile

acid mechanism:
-protonated oxygen renders C=O carbon more electrophilic

favorable nucleophiles:
H2O, CH3OH, HCl, HBr, H2SO4

Front 7

What are characteristics of nucleophilic addition of hydride reagents and Grignard reagents to ketones and aldehydes?

Back 7

Grignard reagents:
-give tetrahedral magnesium alkoxide intermediate
-hydrolyzed to produce alcohol
-react like carbanion

Hydride reagents:
-nucleophilic addition of a hydride ion
-LiAlH4 and NaBH4 give hydride ion

Front 8

What are characteristics of nucleophilic addition of amines?

Back 8

Imine formation:
-primary amines add to aldehydes and ketones to form imines (R2C=NR)
-Carbinolamine tetrahedral intermediate
-elimination of water to form C=Nu bond
-common biological intermediates

Enamine formation:
-secondary amines add to ketones or aldehydes to form enamines (R2N-CR=CR2)
-carbinolamine tetrahedral intermediate
-elimination of water yields iminum ion
-loss of proton from alpha carbon yields enamine
-ene + amine = unsaturated amine

BOTH REACH MAXIMUM RATE AT pH 4-5

at ph > 5:
-slow because insufficient H+ present to protonate carbinolamine -OH to yield better leaving group -OH2+

at ph < 4:
-basic amine nucleophile is protonated so intial nucleophilc addition cannot occur

Front 9

What are characteristics of nucleophilic addition to alcohols?

Back 9

Acetal formation:
-acid catalyzed
-hemiacetal tetrahedral intermediate is formed by loss of proton, hydroxy ether analagous to gem diol
-protonation of hemiacetal makes better leaving group, loss of OH2+ leaves oxonium ion, R2C=OR+
-nucleophilic addition of 2nd alcohol gives protonated acetal
-deprotonation leads to neutral acetal

addition of ethylene glycol gives CYCLIC acetal

common in carbs give cyclic hemiacetals (glucose)

Front 10

What is the Wittig reaction?

Back 10

converts aldehydes and ketones into alkenes

phosphorous ylide (phosphorane) (R2C-P(C6H5)3) adds to aldehyde or ketone to yield alkoxide ion intermediate

4 member ring is formed by O-P bond formation

decomposes to give alkene and triphenylphosphine oxide

Phosphorous ylides are formed by SN2 reaction of primary and some secondary alky halides with triphenylphsophine (Ph)3P followed by treatment with base

used to form numerous pharmaceuticals (Vit A)

Front 11

What is the Cannizzaro reaction?

Back 11

exception to characteristic ketone and aldehyde reaction which cant have tetrahedral intermediates with -H and -R as leaving groups

OH adds to aldehyde to give tetrahedral intermediate

H- ion is expelled as leaving group

in biology:
NADH donates H- ion to aldehydes and ketones

Front 12

What are characteristics of conjugate nucleophilic addition to alpha, beta unsaturated aldehydes and ketones? What is a biological example for carboxylic acid?

Back 12

can add directly to carbonyl of aldehydes and ketones for 1,2 addition

can add to conjugate C=C bond adjacent to carbonyl for 1,4 addition

initial product of conjugate addition is a resonance stabilized enolate ion

biological reaction:
-water is added to alpha, beta unsaturated carboxylic acid in citric acid cycle
-cis aconitate is converted to isocitrate

Front 13

How do amines add to alpha, beta unsaturated aldehydes and ketones?

Back 13

primary and secondary amines add to alpha, beta unstaturated aldehydes and ketones to yield BETA amino aldehydes and ketones

both 1,2 and 1,4 occur