carbonyl by stariya


									                           Outline of Aldehyde and Ketone Chemistry
J. Neitzel March 5, 2003
1. Nomenclature: Two systems in use for aldehydes: Normal IUPAC name with –al as
   suffix. Aldehydes rank higher in priority than any other functional group we have
   seen to date, but below carboxylic acids. Ex. 2-hydroxypropanal. Aldehydes are also
   named as a variant of the related carboxylic acid-examples include acetaldehyde
   (acetic acid) and benzaldehyde (benzoic acid). Finally, if the –CHO group is attached
   to a ring it is named as a –carbaldehyde suffix to the attached ring.
   Ketones can be named as normal IUPAC (2-butanone) or by listing the two attached
   groups to the carbonyl and adding the work ketone (acetone=dimethyl ketone). In
   molecules with groups of higher priority the ketone functional group is labeled as an
   –oxo- group. (example-pyruvic acid is 2-oxopropionic acid). Two commonly used
   labels for attachments are formyl for the –CHO group and acetyl(Ac-) for the
   –COCH3 (as in acetyl-coenzyme A).
2. Physical properties. More polar than hydrocarbons, less polar than alcohols. Cannot
   form hydrogen bonds with themselves but can with water, so small carbonyl
   compounds have good water solubility.
3. Synthesis:
   A. Oxidation of alcohols (review 12. 4). Secondary alcohols to ketones easy; with
       primary alcohols it is hard to stop at the aldehyde state, so special oxidizing
       agents such as PCC must be used.
   B. Reduction of acid chlorides, esters and nitriles. Cannot easily make aldehydes
       from carboxylic acids, as (Lithium aluminum hydride)LAH will go past the
       aldehyde to the alcohol. By converting the acid to the acid chloride (using the
       same agents, such as thionyl chloride, used to convert alcohols to alkyl halides)
       and weaker reducing agents (lithium tri-tert-butoxy-aluminum hydride or
       diisobutylaluminum hydride p. 720) these forms of carboxylic acids can be
       reduced to aldehydes.
   C. Treating an aromatic ring with aluminum trichloride and the corresponding
       acid chloride (Friedal-Crafts acylation, pp. 672-673), can make aromatic
       ketones. The benzene ring must not have strong electron withdrawing groups such
       as carboxylic acids, nitriles, nitro groups and the like. (Table p. 680)
4. The main reaction to consider in chapter 16 is nucleophilic addition to the
   carbon-oxygen double bond. These additions are often reversible. Aldehydes are
   usually more reactive than ketones due to both steric factors and electronic
5. Examples:
   A. Addition of alcohols to form acetals and hemicacetals. This is a key reaction in
       carbohydrate chemistry, both in the formation of their ring structures and in the
       attachment of other organic molecules as glycosides. Usually done by adding dry
       HCl to a solution of alcohol and carbonyl compound. Cyclic acetals and
       hemicacetals that make 5- or six-membered rings are unusually stable. These
       addition products are stable to base but come apart in acid. They are valuable
       protecting groups in basic conditions.
   B. Addition of water to form gem-diols. This is usually the form in which the
       carbonyl compound reacts with oxidizing agents. These hydrates can form in both
       acid and base solutions.
   C. Reaction with thiols to form thioacetals. These are not directly important but
      they react with Raney Nickel catalysts and hydrogen gas to convert the
      corresponding carbonyl compound into a hydrocarbon. For example, the best
      way to add a long straight chain alkane to an aromatic ring is to use a Friedal-
      Crafts acylation followed by this reduction method. A major advantage is this
      method does not require acidic or basic conditions.
   D. Addition of derivatives of ammonia. A wide range of ammonia derivatives can
      add to carbonyls –see pages 738-743. These derivatives were long used to identify
      carbonyl compounds and sugars based on their clean melting points. Hydrazones
      and the Wolff-Kishner reduction provide another route to convert carbonyl
      compounds into alkanes. The interconversion of ketones to amine derivatives is a
      key step in metabolism in the exchange of carbon skeletons and nitrogen in cells,
      such as in the breaking down and synthesis of amino acids. These cellular
      reactions usually using enzymes dependent on Pryidoxal phosphate (the active
      form of vitamin B-6).
   E. Addition of hydrogen cyanide. In the lab, the resulting nitrile group can be
      hydrolyzed in acid to give an -hydroxy acid. In nature cyanogenic glycosides in
      plants often contain cyanide in this form. (example-amygdalin in seeds of some
      Rose family fruits).
6. Other important reactions
   A. The Wittig reaction (p 745). This is important as a route to link molecules
      together by using a carbonyl compound and converting the C=O bond into a
      linking C=C bond. There is no ambiguity as to the location of the double bond in
      the product. An alkyl halide containing the two groups to be linked on the side of
      a double bond opposite the carbonyl carbon provides the other carbon atoms. This
      halide is reacted with triphenylphosphine, P(phenyl)3. This is an SN2 reaction,
      with the phosphorus atom acting as the nucleophile. In the second step, a strong
      base removes the proton on the carbon attached to P, to form a phosphorus ylide
      (an ylide is a molecule in which a charge separation between two adjacent atoms
      exists in the stable form.) The partially anionic carbon formed then adds to the
      carbonyl in a nucleophilic addition. Here, the mechanism is not important but you
      should understand how to predict the products or design this synthesis.
   B. Addition of Grignards, organolithiums, and other organometallic
      compounds. (12.5-12.8). In all of these, the organometallic compound can be
      viewed as a source of a carbon anion, which is a strong base and potent
      nucleophile. These carbon nucleophiles readily add to carbonyl compounds. A
       similar reaction is the Reformatsky reaction, in which an organo-zinc compound is formed by an alkyl halide,
       which is  to an ester carbonyl. The organozinc compounds are less reactive than our earlier organometallic
       compounds and will not react with the ester group.
    C. Oxidation of carbonyls. Aldehydes are much easier to oxidize than ketones, and
        can be oxidized by even mild oxidants such as silver oxide. See Tollens’ test page
    D. Reduction of aldehydes and ketones to the corresponding alcohols. Sodium
        borohydride and lithium aluminum hydride are commonly used reducing agents.
8. Review spectroscopy. Note that carbonyl stretches can be used to more carefully
identify the environment around them-see Table 16.3, p. 753

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