Carbonyl Compounds

Carbonyl groups

Aspects of the Carbonyl C=O Bond

  • The C=O group the most important functional group in organic chemistry

  • An extremely large Class of Compounds (Carbonyl Compounds) contains the C=O group

  • aldehyde and ketones do not have good leaving groups

    • only undergo nucleophilic addition reactions

  • acid halides, anhydrides, esters and amides undergo nucleophilic substitution reactions - have good leaving groups.

    Structure and Reactivity

    • Carbonyl compounds show sp2 hybridization leading to planar geometry (120° bond angles).

    • The C=O bond acts as an electrophile due to electronic characteristics.

      • C=O is the central functional group in many biological molecules.

  • The carbon in the carbonyl group is electrophilic due to the polarization of the C=O bond.

    • Oxygen is more electronegative, creating a dipole moment.

    • This makes the carbon susceptible to nucleophilic attack.

  • nucleophile can substitute leaving group - circled blue

Reactions with Carbonyl Groups

  • Nucleophilic Substitution Reactions (Nucleophile attacks replace a leaving group):

    • Requires a good leaving group (LG).

    • Example of good LCs: -OR (alkoxy) > -OH (hydroxy).

  • Nucleophilic Addition Reactions (Addition across the C=O):

    • Example: If there is no good leaving group available, an acid workup is necessary post-reaction.

    • for nucleophilic attacks, aldehyde more reactive than ketone

Y = X, OR, NR2

Carbonyl Group as Electrophile

  • Nucleophilic Substitution Reactions

  • need a good leaving group (LG)

  • an electronegative subsbtuent that can act as a LG (eg. – OR and – Cl)

  • aldehydes & ketones don’t have a good LG (– R and – H are poor LG) so NO nucleophilic subsbtubon reaction

  • Nucleophiles examples

    • H- (hydride)

    • HO- (hydroxide)

    • RMgBr (Grignard ➣ R-)

    • )RLi (alkyl lithium ➣ R-

Identifying the Best Leaving Group

  • The better the leaving group, the easier it can exit the molecule during a reaction.

  • for this reaction to proceed to completion, a group has to leave from the sp3 (tetrahedral) structure

  • A Leaving Group needs to be a stable sink for electron density

  • Leaving group form anions such as Cl-, RO-, and RCO2- that can be expelled from molecules taking their negative charge with them.

  • rules to identify best leaving group

    • neutral molecules or stable anion

    • weaker basic strength of group, better leaving group

    • low pka value of its CA (~<13) - stable

best = Cl-, poor =HO-, awful = H3C-

  • Comparison: Alkoxy (-OR) is generally a better leaving group than hydroxyl (-OH).

    • Hydroxyl groups can turn into bad leaving groups under strong base conditions due to deprotonation which leads to less stability.

halide is the best leaving group

What If There Isn’t a Good Leaving Group?

  • If nucleophilic substitution isn't feasible:

    1. Conduct nucleophilic addition.

    2. Follow-up with an acidic workup to regain reactivity (convert O to -OH).

Functional Groups in Organic Chemistry

Types of Functional Groups

  • Hydrocarbons: Alkanes, alkenes, alkynes

  • Simple Oxygen Compounds: Alcohols, ethers, epoxides

  • Heteroatomics Include: Halogens, nitrogen, sulfur

  • Carbonyl Compounds: Aldehyde, ketone, carboxylic acid, esters, anhydrides, amides

    • **Name Relationships: **

      • Aldehydes (-al)

      • Ketones (-one)

      • Carboxylic acids (-oic acid)

      • Esters (-yl-oate)

      • Amides (-amide)

Characteristics of Carbonyl Groups

Nucleophilic Attack

  • Carbonyl carbons are susceptible to nucleophilic attacks leading to new reaction pathways forming tetrahedral intermediates.

Strong Leaving Groups

  • Good leaving groups tend to have low pKa values (weaker bases = better leaving group).

  • Examples of leaving groups ranked: Cl > HO > H3C (better to worse).

Nucleophilic Substitution Challenges

  • For reactions to progress, leaving groups must be identified and stability must be ensured, otherwise, nucleophilic addition will occur instead.

  • Hydroxyl groups can be poor leaving groups unless transformed in acidic workup conditions.