Fragrant odors Basic building block of housing materials Hormones Digestion Vision 2

Aldehydes & KetonesO

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In General

Fragrant odors Basic building block of housing

materials Hormones Digestion Vision

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In General

Carbonyl group› C=O› Aldehydes

RCH=O Formyl

› Ketones RC=OR’

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Nomenclature

Aldehydes› IUPAC end in “al”› Common end in “aldeyde”› Carbonyl C is always #1› Cyclic cpds

Carbaldehyde is ending for most

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Nomenclature

Aldehydes

CH2 O

O

CH3

O

CH3

O

CH3

methanal(formaldehyde)

ethanal(acetaldehyde)

propanal(propionaldehyde)

butanal(n-butyraldehyde)

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Nomenclature

Aldehydes

3-methylbutanal

3-butenal

2,3-dihydropropanal(glyceraldehyde)

CH3

CH3 O

CH2

O

O

OH OH

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Nomenclature

Aldehydes

cyclopentanecarbaldehyde(formylcyclopentane)

benzenecarbaldehyde(benzaldehyde)

2-hydroxybenzenecarbaldehyde(salicylaldehyde)

O

O

O

OH

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Nomenclature

Ketones› IUPAC end in “one”› Common end in “ketone”› Carbonyl C is never #1, but always gets

low number preference› Cyclic cpds

Carbaldehyde is ending for most

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Nomenclature

Ketones

propanone(acetone)

2-butanone(ethyl methyl ketone)

3-pentanone(diethyl ketone)

CH3

CH3

O

CH3

O CH3

CH3

O CH3

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Nomenclature

Ketones

cyclohexanone

2-methylcyclopentanone

3- buten-2-one(methyl vinyl ketone)

O

O

CH3

CH2

CH3

O

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Nomenclature

Ketones

acetaphenone(methyl phenyl ketone)

benzophenone(diphenyl ketone)

dicyclopropyl ketone

CH3

O

O

O

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Common Aldehydes & Ketones

Formaldehyde› Simplest aldehyde› Manufactured on large scale (8 billion lbs per

annum) from catalyzed oxidation of methanol CH3OH CH2=O + H2

› Gas at RT (bp = -21˚C) but cannot be stored in free state due to polymerization

› Normally 37% soln called formalin (preservative)

› Most used in making of plastics, insulation, particle board, and plywood

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Acetaldehyde› Boils close to RT (bp = 20˚C)› Made by catalyzed oxidation of ethylene

2 CH2=CH2 + O2 2 CH3CH=O

› ~1/2 is oxidized to acetic acid› Remainder used for production of

1- butanol and others.

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Acetone› Simplest ketone› Large scale production like formaldehyde› Produced from oxidation of propene, isopropyl

alcohol, or isopropylbenzene

› ~30% used directly, great solvent, H2O miscible

› Rest used to make stuff like epoxy resins

CH3CH3

O 2

OOHCH3

CH3d ilu te H 2 S O 4

H 2 O

OH

+ CH3

CH3

O

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Quinones› Cyclic conjugate diketones› Simplest is 1,4-benzoquinone› All are colored and are thus used often as

dyes› Alizarin…used to dye the red coats of the

British Army during American Revolution› Vitamin K is required for normal clotting of

blood

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O O

OH

OHO

O1,4-benzoquinone

alizarinOH

CH3

OH

CH3

CH3CH3CH3CH3

vitamin K

Vitamin K

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Synthesis of Aldehydes & Ketones

Oxidation› 1˚ ROH gives aldehyde› 2˚ ROH gives ketone› Cr reagents (PCC) are common

CH3 OHo x id iz in g

a g e n tCH2 O

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Friedel-Crafts Acylation› Recall the rxn?› Makes aromatic ketones

+O

Cl A lC l3

O

+ ClH

benzophenonebenzyl chloride

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Hydration of terminal alkynes› Gives methyl ketones› Catalyzed by acid and mercuric ion

CH3CH

H + , H 2 O

H g + +CH3

CH3

O

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Aldehydes & Ketones in Nature

Many have pleasant odors Used in the perfume industry Extremely expensive to gather from

natural producers Chanel No. 5 (my mom’s fave perfume)

was first perfume to use synthetic organic chemicals in 1921

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Aldehydes & Ketones in Nature

O

O

O

CH3

O

OH

benzaldehyde cinnamaldehyde vanillin

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The Carbonyl Group

C atom is sp2 hybridized Bond angles? C=O bond length is 1.24Å (compared

to 1.43Å for C-O in ROH and ROR O is more EN than C

› Makes a polar bond

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The Carbonyl Group

Most carbonyl reactions are nucleophilic attacks on the carbonyl C

C=C usually is attacked by an electrophile

Due to polarization, physical properties differ from HC’s and ROH’s› bp’s are higher than HC’s, lower than

ROH’s

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The Carbonyl Group

C=O is permanently polarized› Positive part of one molecule is attracted

to negative part of another molecule› Dipole-dipole forces, weaker than H-bonds,

stronger than LDF

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The Carbonyl Group

C=O’s with low MW are soluble in water› Can form H-bonds with water or ammonia

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An Overview of Nucleophilic Addition to Carbonyl Groups

Why does the attack occur? If rxn occurs in hyroxylic solvent (water

or ROH), a proton is usually added to the O

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Carbonyl cpds are weak Lewis bases due to lone pairs on O

Acids can catalyze the addition of weak nucleophiles to carbonyl cpds through protonation

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Nucleophiles add reversibly› Good leaving groups, CB of SA

Nucleophiles add irreversibly› Poor LG, CB of WA

In general, ketones are less reactive than aldehydes› Steric…sp2 v. sp3, R v. H› Electronic…alkyl groups are electron-

donating…ketones have two

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Addition of Alcohols: Formation of Hemiacetals and Acetals

Alcohols are oxygen nucleophiles› OR goes to C, and H goes to O

Because ROH’s are weak nucleophiles, acid catalyst must be used

Product is a hemiacetal› Contains both alcohol and ether on same C

Addition is reversible

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Addition of Alcohols: Formation of Hemiacetals and Acetals

Mechanism of hemiacetal formation has 3 steps› Carbonyl O is protonated by acid catalyst› ROH’s O then attacks carbonyl C› Proton is then lost from resulting +O

Each step is reversible

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Do You Get It?

Write an equation for the formation of a hemiacetal from acetaldehyde, ethanol, and an acid catalyst. Show each step in the rxn mechanism.

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Addition of Alchols: Formation of Hemiacetals and Acetals

Excess ROH means hemiacetals react further to produce acetals

Hydroxyl group of hemiacetal is replaced by an alkoxyl group.

Acetals have two ether groups on same C

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Mechanism of acetal formation

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Mechanism of acetal formation

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Aldehydes that have appropriately located hydroxyl group can exist in equilibrium with a cyclic hemiacetal…5-hydroxypetanal

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Aldehydes that have appropriately located hydroxyl group can exist in equilibrium with a cyclic hemiacetal…5-hydroxypetanal

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Cpds with hydroxyl group 4 or 5 C’s from the aldehyde group tend to form cyclic hemiacetals and acetals due to lack of strain

Carbohydrates

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Ketones also form acetals If a glycol is used, product is cyclic

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Summary› Aldehyde or ketone reacts with ROH› Hemiacetal is formed› Further ROH makes acetal

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Addition of Water: Hydration of Aldehydes and Ketones

Water is an oxygen nucleophile, like ROH’s Can add reversibly

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Addition of Water: Hydration of Aldehydes and Ketones

Aside from formaldehyde hydrate most other hydrates cannot by isolated because they lost water…Keq<1

One exception is trichloroacetaldehyde (chloral)› Forms a stable crystalline hydrate, chloral hydrate,

CCl3CH(OH)2

› Used as a sedative

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Addition of Grignard Reagents and Acetylides

Grignard reagents act as carbon nucleophiles toward carbonyl cpds› Grignard reagent adds irreversibly to the

carbonyl carbon, forming a new C-C bond› Favorable because product (an alkoxide) is a

much weaker base than the starting carbanion› The alkoxide can be protonated to give an

ROH

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Useful route to alcohols› Type of carbonyl determines class of ROH› Formaldehyde gives 1˚ ROH’s

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Other aldehydes give 2˚ ROH’s

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Ketones give 3˚ ROH’s

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Other organometallic cpds like organolithium cpds and aceylides react with carbonyl cpds similarly to Grignard reagents

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Addition of Hydrogen Cyanide: Cyanohydrins

HCN adds reversibly to carbonyl group of aldehydes and ketones to make cyanohydrins› Hydroxyl and cyano group attached to same C› Basic catalyst is needed

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Acetone reacts as follows:

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Cyanohydrins play important role in the defense system of the millipede› Two-chambered gland like the bombadier

beetle› Benzaldehyde cyanohydrin is stored and then

converted to a mixture of benzadehyde and hydrogen cyanide and secreted

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Write an equation for the addition of HCN to benzaldehyde.

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Addition of Nitrogen Nucleophiles

Ammonia, amines, and other related cpds have a lone pair on the N and thus act as a nucleophile toward a carbonyl C

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Reduction of Carbonyl Cpds

Aldehydes and Ketones are easily reduced to 1˚ and 2˚ alcohols, respectively

Metal hydrides used to reduce› Irreversible nucleophilic attack› LiAlH4 or NaBH4

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Reduction of Carbonyl Cpds

The original product is an aluminum alkoxide Then hydrolyzed by water and acid to give

ROH Net result is addition of H across the C=O

O1 . L iA lH 4

2 . H + , H 2 OOH

H

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Oxidation of Carbonyl Cpds

Aldehydes are more easily oxidized than are ketones

Oxidation of an aldehyde gives an acid with the same number of C’s

Oxidizing agents include KMnO4, CrO3, Ag2O

CH3O

C rO 3 , H +

Jo n e s re a g e n tCH3

O

OH

OA g 2 O

O

OH

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Oxidation of Carbonyl Cpds

Tollens Silver Test› Silver-ammonia complex ion is reduced by

aldehydes but not by ketones› If test tube is clean, a mirror forms by the

metallic Ag› Used to “silver” glass using formaldehyde (cheap)

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Keto-Enol Tautomerism

Aldehydes and Ketones may exist as an equilibrium mixture of two forms› Keto and enol forms› Differ in the location of a proton and a double

bond Tautomerism (Greek…same part)

› Structural isomers› Not resonance contributors

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In order for an enol form to exist carbonyl C must have an H attached to the carbon adjacent to the carbonyl group› Known as the -hydrogen and is attached to

the -carbon

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Most simple aldehydes and ketones exist primarily in the keto form› Keto more stable› Acetone, 99.9997% keto form

Phenols have mainly enol form

OH

HH

O

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Carbonyl cpds that do not have an -hydrogen cannot form enols and exist only in keto form

H

O

H

H

O O

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Acidity of -Hydrogens: the Enolate Anion

-Hydrogen is more acidic than normal H attached to a C› Carbonyl C carries a partial + charge, attracting

bonding electrons away from the -H…make it easy for a base to remove the -H

› Resulting anion is stabilized by resonance…enolate anion

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The Aldol Condensation

Enolate anions may act as carbon nucleophiles

Enolate can add reversibly to the carbonyl group of another aldehyde or ketone…known as aldol condensation

Simplest is the combination of two acetaldhyde molecules due to treatment with an aqueous base

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Step 1…base removes -H to form enolate anion

Step 2…enolate anion adds to the carbonyl carbon of another acetaldehyde molecule, making a new C-C bond

Step 3…alkoxide ion form in step 2 accepts a proton from the solvent, thus regenerating the OH- needed for the first step

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3-hydroxyaldehydes are always formed Since -C acts as a nucleophile, the product

always has just one C between the aldehyde and alcohol C’s

Does not matter how long the C chain is in the starting aldehyde

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The Mixed Aldol Condensation

Enolate anion of one carbonyl cpd can be made to add to the carbonyl carbon of another cpd

Consider acetaldehyde and benzaldehyde (has no -H) when treated with base

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Fragrant odors Basic building block of housing materials Hormones Digestion Vision 2