Chapter 17

Aldehydes and Ketones:
Nucleophilic Addition to the Carbonyl Group

Chapter 17 suggested problems: none

Class Notes

  1. Structure and nomenclature

    1. Aldehydes and ketones are carbonyl compounds

      1. Aldehydes

        1. Terminal carbonyls, carbonyl carbon bonded to one carbon atom and to one hydrogen atom

      2. Ketones

        1. Carbonyls carbons bonded to two carbon atoms

      3. Other carbonyl compounds include organic acids, esters, and amides

        1. Carbonyl carbons bonded to a heteroatom - a (usually) nonmetal atom atom other than carbon or hydrogen

    2. Nomenclature

      1. Aldehydes

        1. Longest continuous chain that contains the CHO group

        2. Substitute "al" for "e" for alkane name

        3. Since aldehydes are always terminal groups the carbonyl carbon is C-1

        4. Substitute "dial" if the molecule contains two aldehyde functionalities

          1. Propanedial

          2. 2,4-dimethylpentanedial

          3. Note that the "e" is retained before addition of the suffix

        5. When a formyl group is attached to a ring (-CH=O) the ring name is followed by the suffix "carbaldehyde"

          1. Cyclopentylcarbaldehyde

        6. Acceptable common names of aldehydes (IUPAC - common name)

          1. Methanal - formaldehyde

          2. Ethanal - acetaldehyde

          3. Propanal - propionaldehyde

          4. Butanal - butyraldehyde

          5. Benzenecarbaldehyde - benzaldehyde

      2. Ketones

        1. Longest continuous chain that contains the carbonyl group

        2. Substitute "one" for "e" for alkane name

        3. Number the chain such that the carbonyl carbon is numbered as low as possible

        4. Substitute "dione" if the molecule contains two ketone functionalities

          1. 2,4-pentanedione

          2. Note that the "e" is retained before addition of the suffix

        5. Functional class nomenclature is also acceptable; groups are named alphabetically

        6. Acceptable common names of ketones (IUPAC - common name)

          1. 2-propanone - acetone

          2. 2-butanone - ethyl methyl ketone (commonly MEK or methyl ethyl ketone)

          3. 3-methyl-2-pentanone - isobutyl methyl ketone (commonly MIBK or methyl isobutyl ketone)

  2. Structure and bonding: the carbonyl group

    1. Hybridization - both the C and O are sp2 hybridized

    2. Trigonal planar geometry - flat, 120° bond angles (more or less)

    3. C=O bond length of 122 pm as compared to C-O bond length or abt. 140 pm in alcohols and ethers

    4. There are two resonance structures for the carbonyl group

      2. A is more stable since it avoids charge separation

    5. Carbonyl carbons are stabilized by alkyl substituents, as is the case for other sp2-hybridized carbons (e.g., in alkenes)

      1. Ketones have lower heats of combustion (i.e. more stable)

      2. Relative reactivity is also affected by this feature

  3. Physical properties

    1. Polar bond: can form polar bonds with water, alcohols, and other polar solvents but cannot form hydrogen bonds

    2. BP higher than alkanes, alkenes, alkynes but lower than alcohols

    3. More soluble than alkanes, alkenes, alkynes, but less soluble than alcohols

  4. Sources of aldehydes and ketones

    1. Common natural products - sugars and carbohydrates, other polyfunctional compounds

    2. Oxidation of 1° and 2° alcohols

    3. Ozonolysis of alkenes

    4. Hydration of alkynes

    5. Reduction of organic acids to 1° alcohols and oxidation to aldehydes (difficult in actual practice)

  5. Reactions of aldehydes and ketones

    1. Reduction of carbonyl compounds to hydrocarbons (Carey 12.8)

    2. Reactions with organometallic compounds (Carey 14.6f)

    3. Reduction of carbonyl compounds to alcohols (Carey 15.2)

  6. Principles of nucleophilic addition

    1. In a carbonyl group the C atom is electron-deficient and the O atom is electron-rich

    2. The standard explanation: the electron-deficient C atom makes the carbonyl group susceptible to attack from nucleophiles

      1. "It is the tendency of oxygen to acquire electrons - its ability to carry a negative charge - that is the real cause of the reactivity of the carbonyl group toward nucleophiles. (The polarity of the carbonyl group is not the cause of the reactivity; it is simply another manifestation of the electronegativity of oxygen.)" (M&B:629)

    3. Because the carbonyl group is flat it is open to attack either from above or below and perpendicular to the plane of the group

      1. The geometry change of the carbonyl carbon from trigonal to tetrahedral can result in steric effects, depending on the size of the attached "R" groups, but steric effects play far less of a role than in the pentavalent transition state of SN2 reactions

      2. If acid is present protonation of the carbonyl O can occur

        1. This stabilizes the transition state by permitting the O atom to accept the pi electrons without having to become negatively charged

    4. Aldehydes are more reactive toward nucleophilic addition than ketones due to a combination of electronic and steric effects

      1. Ketones contain two alkyl groups whereas aldehydes have only one (potential for steric hindrance)

      2. Alkyl groups are electron-releasing which destabilizes the transition state by intensifying the negative charge on the O atom

      3. Also, since alkyl groups stabilize the carbonyl group, the more stable the reactant the greater then activation energy that must be surmounted for reaction to occur

  7. Hydration of aldehydes and ketones

    1. The elements of water add to the carbonyl forming a geminal diol

    2. The reaction is faster in acidic or basic than in neutral solution

    3. Base-catalyzed hydration

      2. Step 1 (rate-determining): attack of carbonyl carbon by hydroxide ion and formation of tetrahedral alkoxide intermediate

      3. Step 2: alkoxide intermediate attacks water and abstracts proton, regenerating hydroxide ion

    4. Acid-catalyzed hydration

      2. Step 1: protonation of carbonyl oxygen

      3. Step 2 (rate-determining): addition of water to carbonyl carbon

      4. Step 3: proton transfer to water

  8. Cyanohydrin formation

    1. Cyanohydrins: compounds with a cyano group and a hydroxyl group bonded to the same carbon

    2. Reasons for interest in cyanohydrin formation

      1. Formation of new carbon-carbon bond

      2. The cyano group can be converted to an amine functionality

      3. The cyano group can be hydrolyzed with formation of alpha-hydroxy or unsaturated carboxylic acids

    3. Mechanism

      2. Step 1: attack by negatively-charged cyanide carbon on carbonyl carbon and subsequent alkoxide intermediate formation

      3. Step 2: alkoxide intermediate attacks HCN and abstracts proton with regeneration of cyanide ion

  9. Acetal formation

    1. Geminal diethers synthesized through the reaction of aldehydes with two equivalents of anhydrous alcohol and a bit of anhydrous HCl

      1. Definitions: hemiacetals, acetals, hemiketals, and ketals

      2. Ketones are generally poor candidates for acetal formation using this particular process (steric factors?) although they generally respond well to reaction with ethylene glycol and cyclic acetal formation

      3. Hemiacetals are extremely unstable (similar to gem-diols), but acetals are extremely stable so the formation of the acetal drives the equilibrium to the product side of the reaction

        1. The reaction is often performed in benzene, which forms an azeotrope with water and drives the reaction toward product

    2. Mechanism

      1. Step 1: protonation of the carbonyl oxygen and formation of the hemiacetal by nucleophilic addition to the carbonyl carbon

      2. Step 2: formation of carbocation intermediate, which is stabilized by the resonance form in Step 3. in which there is a positively charged oxygen atom with a full octet of electrons

      3. Step 3: attack of the carbocation intermediate by a nucleophile (alcohol) and subsequent acetal formation

    3. Cyclic hemiacetals are formed when a compound (e.g., pentoses and hexoses) contain both hydroxyl and carbonyl group

      1. Hydroxyl oxygen atom attacks carbonyl carbon and forms ring

    4. Hemiacetal/acetal formation is an acid-catalyzed reversible reaction

      1. Equilibrium: RCOR + ROH <=> hemiacetal/acetal + water

      2. To drive conversion of acetal to carbonyl compound, simply add excess water

    5. Acetals as protecting groups

      1. Since carbonyls react easily and reversibly with alcohols to form acetals, carbonyl groups can be protected in reactions in which the carbonyl might otherwise be altered

      2. Examples of reagents which can attack carbonyls include hydride reducing agents, organometal compounds, etc.

  10. Reactions with primary amines: imines

    1. Definitions

      1. Primary, secondary, and tertiary amines

      2. Imines: C=N compounds

  11. Reactions with secondary amines: enamines

  12. The Wittig reaction