Carbonyl Chemistry Notes

Unit 3, Part 24: Carbonyl Chemistry

Introduction

  • This unit focuses on carbonyl chemistry.
  • Includes reaction mechanisms and predicting reactions.

Predicting Reactivity

  • Consider electronegativity when predicting reactivity.
  • Any reagent with a metal should be treated as ionic.
  • Consider electrostatic attraction.
  • Identify polarized bonds.
  • Identify the nucleophile and electrophile.
  • The nucleophile will be electron-rich.
  • The electrophile will be the other reagent.
  • Draw curly arrows to represent the movement of electrons.
  • Nucleophilic hydroxide attacks electrophilic carbon next to the leaving group (e.g., Br).
  • Draw products to predict reactivity and understand the full reaction.

Carbonyl Group

  • The carbonyl group (C=O) is a key functional group.
  • The C=O bond is polarized.
  • Features of C=O:
    • It reacts with nucleophiles.
    • Curly arrows are used to represent electron movement.
    • New bond formation occurs, but carbon cannot have 5 bonds.
    • Charge resides on the most electronegative atom (oxygen).

General Two-Step Mechanism: Nucleophilic Addition

  • C=O is polarized with a partial positive charge (δ+) on carbon and a partial negative charge (δ-) on oxygen.
  • Step 1 (Addition): A nucleophile (Nuc-) approaches at approximately 110° to the plane of C=O and adds to the carbon, resulting in nucleophilic addition. A tetrahedral alkoxide ion intermediate is formed.
  • Step 2 (Protonation): A proton (H+) from water or HCl is added, protonating the oxygen (O-) to form an alcohol.

Aldehydes vs. Ketones

  • Aldehydes have one large substituent bonded to the C=O.
  • Ketones have two substituents bonded to the C=O.
  • Aldehydes are generally more reactive than ketones because the aldehyde C=O is more polarized than the ketone C=O.
  • The transition state for addition is less crowded and lower in energy for an aldehyde than for a ketone.

Curly Arrows: Revision

  • In a reaction, a curly arrow represents the movement of two electrons.
  • Three allowable curly arrows:
    • Bond to lone pair
    • Lone pair to bond
    • Bond to bond
  • Do not violate the octet rule.
  • Never draw curly arrows coming together; electrons flow in one direction from an electron-rich area to an electron-poor area.

Reaction Mechanism

  • A reaction mechanism describes how a reaction occurs:
    • Which bonds are broken and which new ones are formed.
    • The order and relative rates of the various bond-breaking and bond-forming steps.
    • If in solution, the role of the solvent.
    • If there is a catalyst, the role of the catalyst.
    • The position of all atoms and the energy of the entire system during the reaction.

Developing a Reaction Mechanism

  • Design experiments to reveal details of a particular chemical reaction.
  • Propose a set (or sets) of steps that might account for the overall transformation.
  • A mechanism becomes established when it is shown to be consistent with every test that can be devised.
  • This does not mean that the mechanism is correct, only that it is the best explanation we are able to devise.

Why Reaction Mechanisms?

  • They are the framework within which to organize descriptive chemistry.
  • They provide intellectual satisfaction derived from constructing models that accurately reflect the behavior of chemical systems.
  • They are tools with which to search for new information and new understanding.

Nucleophilic Addition Reactions

  • General mechanism: Nucleophilic addition reaction.
  • Strong nucleophiles:
    • Cyanide ion, leading to cyanohydrin formation.

Grignard Reagent

  • A carbon–magnesium bond is strongly polarized, so a Grignard reagent reacts as RCH2−MgCl+RCH_2^-MgCl^+.

Weak Nucleophiles

  • Reaction with alcohols.

Addition of Alcohols to C=O

  • Excess of alcohol, removal of water favors acetal/ketal formation.
  • Excess of water favors hydrolysis back to the carbonyl.
  • Mechanism:
    • Step 1: Protonation of C=O to create a stronger electrophilic center.
    • Step 2: Addition of alcohol.
    • Step 3: Protonation and removal of H2O.
    • Step 4: Addition of alcohol (one more time).
    • Step 5: Deprotonation (release of H+H^+.
  • Aldehyde gives acetal.
  • Ketone gives ketal.

Addition of Amines to C=O

  • RNH<em>2RNH<em>2 adds to C=O to form imines, R</em>2C=NRR</em>2C=NR (after loss of H2OH_2O).
  • Reaction type: Nucleophilic Addition then Elimination (not substitution!).
  • Imine formation mechanism shares similarities with acetal formation.

Imine Derivatives

  • Brady’s reagent is used to form imine derivatives.
  • Core Concepts:
    1. Understand the general mechanism for nucleophilic addition to the carbonyl (aldehyde/ketone) group.
    2. Apply nucleophilic addition to the carbonyl group to the formation of hemiacetals/hemiketals and acetals/ketals.
    3. Explain and show how acid-catalysis accelerates acetal/ketal formation.
    4. Apply the concept of equilibria to show acetal/ketal formation is reversible, allowing the hydrolysis of acetals/ketals.
    5. Use curly arrow notation to predict the product of nucleophilic addition of other nucleophiles.