Chemistry 332 - Winter 1997

Chapter 9 - Carbonyl Compounds

Carbonyl Functional Groups

usually subdivided into two families:
aldehydes and ketones

• both R groups are C or H

carboxyl derivatives

• X is some electronegative element
• (halogen, O, N, S, others)
• covered in Chapter 10

The Carbonyl Group - Structure and Properties

• polar C=O double bond
• O is nucleophilic
  reacts with acids & electrophiles
• C is electrophilic
  reacts with Lewis bases and nucleophiles

Aldehyde Nomenclature

• IUPAC: alkanal
  -al suffix, with carbonyl assumed #1 in parent chain
  
  (R)-3-methylpentanal
  
  -carbaldehyde suffix
  (if aldehyde can't be part of the parent)
  e.g., cyclohexanecarbaldehyde
  
• common nomenclature:

formaldehyde
acetaldehyde
propionaldehyde
butyraldehyde
benzaldehyde

Ketone Nomenclature

• IUPAC: alkanone

-one suffix, with number
2-hexanone

-oxo- prefix if necessary
(when it must be a substituent within the parent,
because another functional group takes higher priority
- such as aldehyde)

5-oxoheptanal

acyl- as prefix if necessary
(when the carbonyl isn't be part of the parent)

acetyl
benzoyl

benzoylcyclohexane

• common nomenclature:

dialkyl ketone
acetone
acetophenone
benzophenone

Nomenclature examples:

2-ethyl-4-methylhexanal

1,3-cyclohexanedione

Aldehyde Syntheses

• oxidation of primary alcohols with PCC

Ketone Syntheses

• oxidation of secondary alcohols

with KMnO₄, CrO₃, PCC, Na₂Cr₂O₇

• hydration of terminal or symmetrical alkynes

(other alkynes give mixtures)

• Friedel-Crafts acylation of aromatics

Oxidation of Aldehydes

• very sensitive to oxidation
  (slow reaction with air by a radical chain mechanism)
• Tollen's test
  Ag⁺ in aqueous ammonia reduced to metallic silver (mirror)

Nucleophilic Addition to Carbonyls

the major reaction of carbonyl compounds

General Trends:

• aldehydes more reactive than ketones
  (due to steric hindrance with ketones)
  
  
• aromatic carbonyls less reactive than aliphatic
  (due to conjugation effects)
  
  
• a large variety of nucleophiles can undergo addition reactions

O nucleophiles: OH^-, H₂O, ROH
N nucleophiles: NH₃, RNH₂
H nucleophiles: LiAlH₄, NaBH₄
C nucleophiles: CN^-, RLi, RMgX

Acid Catalysis of Nucleophilic Addition

• protonation generates a more reactive electrophile
  (carbon becomes more receptive to nucleophiles)

• works well to enhance reactivity with weak nucleophiles
• doesn't work for nucleophiles that protonate readily

Hydration Reactions

• as in hydration of C=C double bonds,
  the elements of H and OH are added

• H₂O is the nucleophile
• the product is a geminal diol

Hydration is a reversible equilibrium

• formaldehyde in water is mainly dihydroxymethane
• most other carbonyls have unfavorable equilibria
  (very little gem-diol in aqueous solution)
• reaction rate is slow at pH 7
  but faster in acid or in base (catalysis)

Base-Catalyzed Hydration

• OH^- is a strong nucleophile

Acid-Catalyzed Hydration

• H⁺ acts as a catalyst

Comparison of acid and base catalytic effects

• in base, a strong nucleophile is generated by deprotonation
• in acid, the carbonyl is made more receptive to a weak nucleophile
• note that you can't have both at the same time
  (although nature comes close with some enzyme catalysts)

Alcohol Additions

• reversible addition gives a hemiacetal, which is usually unstable

• the hemiacetal undergoes acid-catalyzed substitution (S_N1) to an acetal

• ketal (and hemiketal) are terms often used for the corresponding products from ketones
  
  
• reversible acid-catalyzed equilibrium
  pushed forward by removal of water
  reversed by addition of excess water (hydrolysis)

Acetals as protecting groups

• ether functional groups are mainly unreactive
• but easily removed by acid hydrolysis
  
  
• protecting groups temporarily "cover up" a reactive carbonyl group
• usually to avoid unwanted reactions during other synthetic steps

Amine Additions

• reversible addition gives an aminol, which is usually unstable

• the aminol dehydrates to an imine under acid catalysis

• acid-catalysis limited to mild pH ranges (typically 4 - 6)
• otherwise the amines are all protonated and no longer nucleophilic

Wolff-Kishner reduction

• method for removal of a carbonyl group (to an alkane)

Hydride Additions

• reductions by LiAlH₄ or NaBH₄ are additions of "H^-"
  
  
• irreversible

Carbon Additions

• cyanide additions gives cyanohydrins

• organometallic reagents (nucleophilic carbon)
  
  
• add a new C-C bond and make alcohols
  
  
• addition is irreversible

• Grignard + formaldehyde --> 1° alcohol
  
  
• Grignard + aldehyde --> 2° alcohol
  
  
• Grignard + ketone --> 3° alcohol
  
  
• useful synthetic reaction
  a new C-C bond is formed
  builds up a larger carbon skeleton
  
  
• Grignard reagents are incompatible with most other polar functional groups
  (OH, COOH, NH₂, etc.) and with atmospheric water and oxygen

Natural Cyanohydrins

• some organisms use cyanohydrins to release toxic HCN as a defense mechanism

Glucose Hemiacetals

• the major form of most sugars in aqueous solution is as cyclic hemiacetal isomers
  (covered in Chapter 14)

Glucose Acetal Polymers (Starches and Cellulose)

• the storage form of glucose in animals (starches)
  and in plants (cellulose - structural material)