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Overview of the Reactions of Carbonyl Compounds


									  Overview of the Reactions of
     Carbonyl Compounds
• Topical Outline of Coverage
  – I. Kinds of Carbonyl Compounds.
  – II.Polarity of the Carbonyl Functional
  – III.General Reactions of Carbonyl
     • A.   Nucleophilic Addition Reactions
     • B.   Nucleophilic Substitution Reactions
   Kinds of Carbonyl Compounds
• All carbonyl compounds contain the acyl group


• where the (R) residue bonded to the carbonyl
  maybe alkyl, aryl, alkenyl, or alkynyl. The
  different kinds of carbonyl compounds arise from
  the nature of the other residue bonded to the
  carbonyl group.
    Kinds of Carbonyl Compounds

            X = H then aldehyde
            X= R then ketone
    O       X = OH then carboxylic acid
            X = Cl then acid chloride
    C       X = OR then ester (cyclic esters = lactones)
R       X   X = OCOR then acid anhydride
            X = N then amide (cyclic amides = lactams)
   Categories of Carbonyl Compounds
• Carbonyl
  may be
  grouped into
  two broad
  based upon
  whether or
  not they take
  part in
        Aldehydes and Ketones

                  R       X

• Aldehydes and Ketones - X = H and R
  respectively ; these carbonyl compounds do
  not undergo nucleophilic substitution
  reactions. That is to say, the H and R groups
  are never substituted by other groups. Both H-
  and R- make poor leaving groups.
Carboxylic Acids and their Derivatives

                 R       X

• Carboxylic acids and their derivatives –
  X = some heteroatom (O, Cl, or N).
  Nucleophilic substitution reactions are
  possible for these carbonyl compounds
  because the electronegative heteroatom can
  stabilize a negative charge and form good
  Leaving Groups.
         Polarity of the Carbonyl
• The carbon-oxygen double bond of the
  carbonyl group is extremely polarized in the
  direction of the highly electronegative oxygen.
  This polarization is responsible for the
  characteristic reactions of carbonyl compounds

      - :O:           nucleophilic oxygen reacts with
                       acid and other electrophiles
      + C
                        electrophilic carbon reacts with
                        bases and other nucleophiles
     General Reactions Of
     Carbonyl Compounds

• Nucleophilic Addition Reactions

• Nucleophilic Acyl Substitution
  Nucleophilic Addition Reactions –
             Chapter 09
• There are two different ways in which a nucleophile can add
  to a carbonyl compound. Each way leads to a different
  nucleophilic addition reaction but the mechanisms for both
  reactions involves the same 1st step.
• In this step, the nucleophile bonds to the carbonyl carbon
  and thereby causes a carbon-oxygen bond to break. The
  carbonyl carbon rehybridizes from sp2 to sp3 and the
  carbonyl oxygen becomes negatively charged. At this point
  the tetrahedral intermediate can either be protonated to form
  an alcohol (NaBH4, LiAlH4, or Grignard Reduction) or a
  non-bonded e- pair on the nucleophile can be used to form a
  second bond to the carbonyl carbon. The new bond
  formation causes expulsion of the carbonyl oxygen as H2O.
        First Type of Nucleophilic
• Alcohol Formation –
  Ketones and
  Aldehydes react with
  NaBH4, LiAlH4, and
  Grignard reagents to
  form alcohols
Second Type of Nucleophilic Addition

• Imine formation -
  Ketones and
  Aldehydes react
  with 1o amines to
  form imines .
    Nucleophilic Acyl Substitution –
    • Theses reactions do not apply to aldehydes
      and ketones. These reactions involve the
      substitution of the nucleophile for the X
      residue of the carbonyl compound.

    O         Nu-              O
    C                          C          +        X-
R        X                 R       Nu
Nucleophilic Acyl Substitution
        Carboxylic Acid Derivatives

              X = H then aldehyde
              X= R then ketone
    O         X = OH then carboxylic acid
              X = Cl then acid chloride
    C         X = OR then ester (cyclic esters = lactones)
R       X     X = OCOR then acid anhydride
              X = N then amide (cyclic amides = lactams)
    Carboxylic Acid Derivatives
• These all have an acyl group bonded to Y, an
  electronegative atom or leaving group
• Includes: Y = halide (acid halides), acyloxy
  (anhydrides), alkoxy (esters), amine (amides).
      General Reaction Pattern
• Nucleophilic acyl substitution
Nucleophilic Acyl Substitution-The
• Carboxylic acid
  derivatives have an acyl
  carbon bonded to an
  electronegative group
  Y that can leave
• A tetrahedral
  intermediate is formed,
  then the leaving group
  is expelled to generate a
  new carbonyl
  compound, leading to
      Substitution in Synthesis
• We can readily convert a more reactive acid
  derivative into a less reactive one
• Reactions in the opposite sense are possible but
  require more complex approaches

             Found in Nature
       Reactions of Acid Halides
•   Nucleophilic acyl substitution
•   Halogen replaced by OH, by OR, or by NH2
•   Reduction yields a primary alcohol
•   Grignard reagent yields a tertiary alcohol
  Reactions of Acid Anhydrides
• Similar to acid chlorides in reactivity
          Reactions of Esters
• Less reactive toward nucleophiles than are acid
  chlorides or anhydrides
• Cyclic esters are called lactones and react
  similarly to acyclic esters
Chapter 09. Aldehydes and Ketones:
 Nucleophilic Addition Reactions
• Aldehydes are carbonyl compounds having at least
  one hydrogen attached to the carbonyl carbon.

            O               C                  C
                                           H       H
 propanal           Benzaldehyde         formaldehyde
• Ketones are carbonyl compounds having two
  alkyl fragments attached to the carbonyl carbon.

                                CH3       O
CH3 C CH3                             CH3 C CH2 CH3
2-propanone      acetophenone           2-butanone
   Naming Aldehydes and Ketones
• Aldehydes are named by replacing the terminal -e
  of the corresponding alkane name with –al
• The parent chain must contain the CHO group
   – The CHO carbon is numbered as C1
• If the CHO group is attached to a ring, use the
  suffix carbaldehyde
Names of more Complex
              Naming Ketones
• Replace the terminal -e of the alkane name with –
• Parent chain is the longest one that contains the
  ketone group
   – Numbering begins at the end nearer the carbonyl
  Ketones with Common Names
• IUPAC retains well-used but unsystematic names
  for a few ketones
        Preparation of Aldehydes and
• Preparing Aldehydes
• We have already discussed two of the best methods of
  aldehyde synthesis. These are oxidation of primary
  alcohols, and oxidative cleavage of alkenes. Oxidize
  primary alcohols using pyridinium chlorochromate
               Preparing Ketones
• Ketones may be prepared by the oxidation of
  secondary alcohols. A wide range of oxidizing can
  accomplish this purpose. Some of these are: Jones
  reagent (CrO3 in aqueous sulfuric acid), sodium
  chromate (Na2CrO4) and potassium permanganate
                     OH                                   O

                                   acetic acid

                      C(CH3)3                              C(CH3)3
            4-tert-butylcyclohexanol             4-tert-butylcyclohexanone
     Prep. Of Ketones by Ozonolysis
               of Alkenes
• Ozonolysis of alkenes yields ketones if one of the
  doubly bonded carbons is itself bonded to two
  alkyl groups.
   Prep. Of Ketones by Hydration of
          Terminal Alkynes
• Methyl ketones can be prepared by the
  Markovnikov addition of water to a terminal
  alkyne. The reaction needs to be catalyzed by
  Hg+2 ion. See Section 4.13 of text.
     Aryl Ketones by Acylation
• Friedel–Crafts acylation of an aromatic ring with
  an acid chloride in the presence of AlCl3 catalyst
  (see Section 5.6)
 Oxidation of Aldehydes and Ketones
• Aldehydes are readily oxidized to carboxylic acid but
  ketones are unreactive towards oxidation except under the
  most vigorous conditions. This difference in reactivity
  towards oxidation lies in the structural difference between
  the two types of carbonyl compounds. Aldehydes are
  more easily oxidized because they posses a hydrogen
  atom bonded to the carbonyl carbon. This hydrogen atom
  can be removed as a proton with the final result being the
  oxidation (loss of hydrogen) from the original aldehyde.
  Ketones have no expendable carbonyl-hydrogen bond.
   Oxidation of Aldehydes and Ketones
• Many oxidizing agents will convert aldehydes to carboxylic
  acids. Some of these are Jones reagent, hot nitric acid and

              O                                O
CH3(CH2)4     C    H             CH3(CH2)4     C    OH

• One drawback to the Jones reagent is that it is acidic. Many
  sensitive aldehydes would undergo acid - catalyzed
  decomposition before oxidation if Jones reagent was used
        A Milder Oxidizing Agent
• For acid sensitive molecules a milder oxidizing
  agent such as the silver ion (Ag+) may be used. A
  dilute ammonia solution of silver oxide, Ag2O,
  (Tollens reagent) oxidizes aldehydes in high yield
  without harming carbon-carbon double bonds or
  other functional groups.
                 Tollens Oxidation

•Note; In this reaction the oxidizing agent is Ag+ and it is
ultimately reduced to Ag(s).
•A shiny mirror of metallic silver is deposited on the inside
walls of the flask during a Tollens oxidation: observation of
such a mirror forms the basis of an old qualitative test for the
presence of an aldehyde functional group in a molecule of
unknown structure.
        Nucleophilic Addition Reactions of
             Aldehydes and Ketones
• Nu- approaches 45° to the plane of C=O and adds to the
  Carbonyl Carbon
• A tetrahedral alkoxide ion intermediate is produced and
  ultimately protonated
• Nucleophiles can be negatively charged ( : Nu) or neutral
  ( : Nu-H)
• If neutral, the nucleophile usually carries a hydrogen atom
  that can subsequently be eliminated and carry away the
  positive charge.
 Relative Reactivity of Aldehydes and Ketones
• Aldehydes are generally much more reactive than ketones.
  There are two reasons for this;
   – Aldehydes are less sterically hindered than ketones. In
     other words the carbonyl carbon of aldehydes is more
     accessibly to attack. The presence of two relatively large
     substituents in ketone hinders the attacking nucleophile
     from reaching the carbonyl carbon.

   –   The + on the carbonyl carbon is reduced in ketones
       because of the ability of the extra alkyl group to stabilize
       a + charge. This ability is emphasized in the stability
       order of carbocations. 3o>2o>1o
        Aldehydes Have A Greater
     Electrophilicity Than Do Ketones
• Aldehyde C=O is more polarized than ketone C=O
• As in carbocations, more alkyl groups stabilize + character
• Ketone has more alkyl groups, stabilizing the C=O carbon
         Addition of H-Y to C=O
• Reaction of C=O with H-Y, where Y is electronegative,
  gives an addition product (“adduct”) and the reaction is
  readily reversible because the electronegative Y is a
  good leaving group.
  Nucleophilic Addition of Alcohols:
         Acetal Formation
• Two equivalents of ROH in the presence of an acid
  catalyst add to C=O to yield acetals, R2C(OR)2
• Alcohols, ROH, fall under the category of Y-H and
  therefore the reaction is reversible.
• Mechanism for
  Formation of
               Uses of Acetals
• Acetals can serve as protecting groups for
  aldehydes and ketones-remember the rxn. is
• It is convenient to use a diol, to form a cyclic
  acetal (the reaction goes even more readily)
 Nucleophilic Addition of Grignard Reagents and
     Hydride Reagents: Alcohol Formation
• Treatment of aldehydes or ketones with Grignard
  reagents yields an alcohol
  – Nucleophilic addition of the equivalent of a carbon
    anion, or carbanion. A carbon–magnesium bond is
    strongly polarized in the direction of the carbon atom, so
    a Grignard reagent reacts for all practical purposes as R:
    and MgX +.
  Mechanism of Addition of Grignard
• R- attacks the carbonyl carbon. The alkoxide
  anion is then protonated by dilute acid.
• Grignard additions are irreversible because a
  carbanion is not a leaving group
             Hydride Addition
• H- attacks the carbonyl carbon. The alkoxide
  anion is then protonated by dilute acid.
• Hydride additions are irreversible because a
  hydride is not a good leaving group
• LiAlH4 and NaBH4 react as donors of hydride ion
Nucleophilic Addition of Amines: Imine Formation
Primary amines (RNH2) add to C=O to form imines, R2C=NR
  (after loss of HOH)
• Mechanism of
  Imine Formation
                   Imine Derivatives
• Addition of amines that have an adjacent atom containing a
  lone pair of electrons occurs very readily, giving useful,
  stable imines
• For example, hydroxylamine forms oximes and 2,4-
  dinitrophenylhydrazine readily forms 2,4-
   – These are usually solids and help in characterizing liquid ketones
     or aldehydes by melting points
   Spectroscopy of Aldehydes and
• Infrared Spectroscopy
• Aldehydes and ketones show a strong C=O peak 1660 to
  1770 cm1
• aldehydes show two characteristic C–H absorptions in the
  2720 to 2820 cm1 range.
      C=O Peak Position in the IR
• The precise position of the peak reveals the exact
  nature of the carbonyl group
• Aldehydes are from oxidative cleavage of alkenes
  or oxidation of 1° alcohols
• Ketones are from oxidative cleavage of alkenes or
  oxidation of 2° alcohols.
• Aldehydes and ketones are reduced to yield 1° and
  2° alcohols , respectively
• Grignard reagents also gives alcohols
• 1° amines add to form imines
• Alcohols add to yield acetals

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