ALDEHYDES AND KETONES

Dr. Sheppard

CHEM 2412

Summer 2015

Klein(2nd ed.) sections: 20.1, 20.2, 20.13, 20.3, 20.4, 20.5, 20.6, 23.6, 20.9, 20.10, 20.12

Outline• Preview of Carbonyl Chemistry• Aldehydes and Ketones

I. Nomenclature Review

II. Properties and Spectroscopy

III. Preparation

IV. Oxidation

V. Nucleophilic Addition

VI. Wittig Reaction

Carbonyl Chemistry Preview• Carbonyl group R C

O

Acyl groupDetermines type of carbonyl

Carbonyl Reactivity• Generally grouped by reactivity

• Aldehydes and ketones• Carboxylic acids and derivatives

Structure of Carbonyls• Hybridization of C?• Bond angle around C?• Hybridization of O?• Nucleophilic or electrophilic?

• Carbonyls are both Lewis acids and Lewis bases

C

O

Reactions of Carbonyls• Nucleophilic Addition

• Aldehydes and ketones• Chapter 20

• Seen already: • Reduction of aldehydes and ketones to form alcohols• Grignard reaction of aldehyde and ketones

Reactions of Carbonyls• Nucleophilic Acyl Substitution

• Carboxylic acids and derivatives• Chapter 21

• Seen already: • Reduction of carboxylic acids and esters to form alcohols• Grignard reaction of esters and acid halides

Aldehydes and Ketones

I. Nomenclature Review

II. Properties and Spectroscopy

III. Preparation

IV. Oxidation

V. Nucleophilic Addition

VI. Wittig Reaction

I. Nomenclature (Review)• Acyclic aldehydes

1. Parent chain contains carbon of CHO

2. Suffix is “-al”

3. CHO carbon is carbon 1 (do not need to show in name)

• Cyclic molecules with –CHO substituents1. -CHO is bonded to carbon 1 of ring

2. Add “carbaldehyde” to end of ring parent name

CH3 CHO

trans-4-methylcyclohexanecarbaldehyde

O

C

H H

O

C

CH3 H H

O

methanal (formaldehyde)

ethanal(acetaldehyde)

3-methylbutanal

I. Nomenclature (Review)• Ketones

• Parent chain contains carbon of carbonyl; suffix is “-one”• Number so carbonyl has lowest number• Cyclic ketones carbonyl is carbon 1 of the ring• Common name system:

• Name both alkyl groups bonded to carbonyl• Add “ketone”

O

2-propanone(acetone or

dimethyl ketone)

O

2-pentanone(methyl propyl ketone)

O

2-methylcyclopentanone

I. Nomenclature (Review)

• Order of precedence of functions• Used when more than one functional group in a

molecule

• Example:

Functional GroupSuffix

(High Precedence)Prefix

(Low Precedence)

-CO2H -oic acid -

-CHO -al formyl-

-C(O)- -one oxo-

-OH -ol hydroxy-

-NH2 -amine amino-Incr

easi

ng p

rece

denc

e

H

OO

3-oxobutanal

II. Spectroscopy of Aldehydes and Ketones: IR

• Absorption at 1650-1750 cm-1 for C=O• Absorptions at 2720 and 2820 cm-1 for aldehyde C-H

II. Spectroscopy of Aldehydes and Ketones: NMR

• Atoms of or bonded to C=O are deshielded• 13C-NMR:

• 1H-NMR: • Aldehyde signal at d9-10; • Hydrogens adjacent

to C=O at d2.0-2.5

II. Spectroscopy of Aldehydes and Ketones: MS

• Molecule fragments on one side of carbonyl (a-cleavage)• Ex: 5-methyl-2-hexanone

• Carbonyls are polar• Intermolecular forces of aldehydes and ketones

• Dipole-dipole• No hydrogen bonding

• Boiling points • Higher than alkanes or ethers; lower than alcohols• Aldehydes typically slightly lower than ketones of the same size

• Solubility• Low MW soluble in water; decreases as MW increases

II. Physical Properties of Aldehydes and Ketones

III. Preparation• Aldehydes

1. Oxidation of primary alcohols with PCC (section 13.10)

2. Oxidative cleavage of alkenes (section 9.11)

3. Hydroboration-oxidation of terminal alkynes (section 10.7)• Uses keto-enol tautomerism

III. Preparation• Aldehydes

4. Reduction of esters (not in Klein)• Reagent = diisobutylaluminum hydride (DIBALH or DIBAH)• Very low temperature prevents reduction to alcohol

III. Preparation• Ketones

1. Oxidation of secondary alcohols (section 13.10)• PCC

• H2CrO4 (CrO3 or Na2Cr2O7)

• KMnO4

2. Oxidative cleavage of alkenes (section 9.11)

III. Preparation• Ketones

3. Hydration of alkynes (section 10.7)

IV. Oxidation• Aldehydes

• Oxidized to carboxylic acids• [O] = H2CrO4 reagents or KMnO4

• Oxidation does not occur with PCC

• Ketones• No oxidation

• Nucleophile attacks electrophilic carbon of carbonyl• Something adds across C=O

• Nucleophile • O, N, H, C• Anion or neutral

V. Nucleophilic Addition

V. Nucleophilic Addition• Reaction may be reversible• Reaction is often acid- or base-catalyzed• Acid: makes the electrophile (carbonyl) more electrophilic

• Base: makes the nucleophile more nucleophilic• For example: ROH + base → RO-

V. Nucleophilic Addition• Mechanism:

• Acidic conditions:

• Basic conditions:

• Product is a racemic mixture if a stereocenter is present

V. Nucleophilic Addition• Which are more reactive, aldehydes or ketones?• Steric effects:

• Aldehydes have more room

for nucleophilic attack

• Electronic effects:• Aldehydes are more electrophilic (larger d+) due to fewer R groups• Exception: benzaldehyde stabilizes d+ through resonance

V. Nucleophilic Addition• Oxygen nucleophiles

1. Water • Aldehyde/Ketone + water → geminal diol (hydrate)

• Hydrates are unstable and rarely isolated• Exception = formaldehyde hydrate (formalin)

V. Nucleophilic Addition• Acid or base catalyst needed because water is a weak nucleophile

• Acid:

• Base:

V. Nucleophilic Addition• Oxygen nucleophiles

2. Alcohols

• Mechanism 20.5 page 941 in Klein• Two nucleophilic additions and lots of proton-transfer reactions

• Alcohol is usually solvent (present in excess), so equilibrium favors product

• Water must be removed as it forms to prevent reverse reaction• Acetal + H2O → aldehyde/ketone

O

C RRR'OH

acid or base

OH

C RRR''OH

acid

OR'

hemiacetal

OR''

C RR

OR'

acetal

+ HOH

V. Nucleophilic Addition• Formation of acetal

V. Nucleophilic Addition• Applications of hemiacetals/acetals

1. Carbohydrates• Haworth structure

• Formation of glycosidic bonds

V. Nucleophilic Addition• Applications of hemiacetals/acetals

2. Carbonyl protecting groups• Convert aldehyde/ketone to acetal

• Acetals are unreactive to bases, Grignard reagents, reducing agents

• Acetals are reactive to aqueous acid

R C R

O

C OR

OR

ROH ROH

H+ H+R C R

O

HOCH2CH2OH

H+C O

O

CH2

CH2

V. Nucleophilic Addition• How can this reaction occur?

• Need to protect ketone so ester (only) can be reduced

V. Nucleophilic Addition• Draw a synthetic scheme for the following reaction

H

OO

H

O HO CH3

V. Nucleophilic Addition• Nitrogen nucleophile

1. Ammonia and 1° amines• Product = imine (Schiff base)• Acid-catalyzed

O

+ CH3CH2NH2H+

N

CH2CH3

+ H2O

O

+ NH3

H+N

H

+ H2O

V. Nucleophilic Addition• Mechanism

• Nucleophilic addition of NH3 or RNH2, followed by loss of water

V. Nucleophilic Addition• Ex: 2,4-dinitrophenylhydrazine

V. Nucleophilic Addition• Imines can be reduced to amines

• [H] = H2, Ni or

LAH or

NaBH4 or

NaBH3CN

• Overall process = reductive amination (section 23.6)• Carbonyl + ammonia → imine → 1° amine• Carbonyl + 1° amine → imine → 2° amine

[H]

C

N

CH

NH

V. Nucleophilic Addition• Reductive amination:

V. Nucleophilic Addition• Draw the reductive amination for the reaction of

acetaldehyde and methylamine.

V. Nucleophilic Addition• Nitrogen nucleophile

2. 2° amines yield enamines• We will not discuss this reaction

3. 3° amines• Do not react with carbonyls

V. Nucleophilic Addition• Nitrogen nucleophile

4. Hydrazine (H2N-NH2)

• React the same as R-NH2

• Product = hydrazone (as seen with 2,4-DNP)• If reaction is run in base, imine is reduced

• Wolff-Kishner Reduction

O

+ H2OH2NNH2

N

NH2

V. Nucleophilic Addition• Hydrogen nucleophiles

• Hydride ion from NaBH4 or LiAlH4 (reduction reactions)

• Aldehyde → primary alcohol• Ketone → secondary alcohol

V. Nucleophilic Addition• Carbon nucleophiles

1. Grignard reagent (R:- +MgX)

2. Cyanide ion (-:C≡N); product = cyanohydrin

3. Acetylide ion (R-C≡C:-)• Can act in the same manner as cyanide ion

4. Wittig reagent ( )Ph3P CR2

VI. Wittig Reaction• Ketone/aldehyde → alkene• A carbon-carbon bond-making reaction

• Phosphonium ylide:• Neutral molecule with opposing charges on adjacent atoms

• A carbon nucleophile• Formed from the reaction of Ph3P: (a good nucleophile) with a 1° or

2° alkyl halide

Ph3P CR2 Ph3P CR2

VI. Wittig Reaction• Formation of ylide:

• Mechanism:

• In second step, weakly acidic H atoms can be removed with a strong base (NaNH2, NaH, BuLi)

• Reaction of ylide and carbonyl:

• Oxaphosphetane can be isolated at low temperature• Driving force for decomposition of ring is formation of strong P=O bond

VI. Wittig Reaction

VI. Wittig Reaction• How could you make this alkene using the Wittig reaction?

• Do Wittig reaction handout

HCH3

Synthesis Problem• Propose a synthesis of butane starting with ethanol. Use

the Grignard reaction.

• Propose a synthesis of butane starting with ethanol. Use the Wittig reaction.

Synthesis Problem• Show reagents and experimental conditions necessary to

bring about each of the following conversions:

a)

b)

OH

NEt

OH OH

O