Biological Chemistry 1A - Carbonyl Chemistry

Biological Chemistry 1A - Carbonyl Chemistry

• Learning Outcomes: Identify carbonyl functional groups, explain their properties, predict reactivity, draw reaction mechanisms using curly arrows, describe Fehling's test, iodoform test, and alkyl halide tests.

Course Content

• Lecture 1: Carbonyl functional groups, drawing mechanisms, resonance structures.
• Lecture 2: Oxidation of alcohols, carbonyl reactivity (vs alkenes), nucleophilic addition, activation of carbonyl groups, Fehling's, lodoform and AgNO₃ test, C-C and C-H bond formation, C=O bonds to C≡N bonds.
• Lecture 3: Fehling's, lodoform and AgNO₃ test. C-C and C-H bond formation, C=O bonds to C≡N bonds.
• Lecture 4: Carboxylic acid derivatives, hydrolysis
• Lecture 5: Ester hydrolysis, reactivity of esters vs amides.
• Lecture 6: Revision session.

Recommended Reading

• Standard organic chemistry textbook - by Jonathan Clayden, Nick Greeves, and Stuart Warren
• Chemistry for the Biosciences - by Jonathan Crowe & Tony Bradshaw.
• Textbooks provide a fantastic introduction and exceptionally well-explained concepts.

Why Care About Organic Reactions?

• Organic chemistry is fundamental to life (biomolecule synthesis).
• Biochemical processes mimic organic lab reactions.
• Understanding these reactions is essential for understanding biological processes' underlying chemistry

Understanding Reactivity and Reaction Mechanisms

• Molecules are constantly colliding and reacting to form new molecules.
• Activation energy is required for molecular collisions to initiate reactions.
• Most organic reactions involve interactions between filled and empty orbitals or charge interactions.
• Curly arrow mechanisms depict electron movement during reactions.
• Covalent bonds are formed and broken during reactions.

Reacting Species (Nucleophiles and Electrophiles)

• Nucleophiles are electron-rich species, donating electrons.
• Electrophiles are electron-poor species, accepting electrons.
• Examples of nucleophiles include -OH, H₂O, and :HC₂CH₂OH.
• Examples of electrophiles include H₃COCH₃, and R−R.
• Orbital overlap is essential for a reaction to succeed.

Important Concepts Related to Organic Chemistry Mechanisms

• Electron movement: Electrons move from areas of high electron density (nucleophiles) to areas of low electron density (electrophiles).
• Curly arrows: Used to represent the movement of electron pairs in organic reactions. "Fish hook" curved arrow represents a single electron.
• Reaction Arrows: Show the direction of the reaction flow from reactants to products in chemical reactions.
• Equilibrium Arrows: Show reversible reactions where products can reform reactants.
• Resonance Arrows: Used to depict different representations of the same molecule (resonance structures).
• Proton (H⁺) and Hydride (H⁻) are considered as electrophiles and nucleophiles, respectively.

Reactivity Differences Between H⁺ and H⁻

• Proton is an electrophile (accepts electrons)
• Hydride is a nucleophile (donates electrons)
• Hydride and protons have very different reactivity.

Why Should You Care About Carbonyl Chemistry?

• Carbonyl group is central in organic chemistry.
• It's used as a precursor to many other functional groups.
• Carbon-carbon bond forming reactions build organic molecules' frameworks.
• The carbonyl group is present in numerous biologically important molecules (e.g., Progesterone, Ibuprofen, Cocaine.).

Coca-Cola History

• In the past, Coca-Cola contained cocaine.
• Initially, cocaine was extracted from the coca leaf.
• Present in past versions, but not currently.

Carbonyl Containing Functional Groups

• Aldehydes and ketones.
• Carboxylic acid derivatives (acids, anhydrides, chlorides, esters, amides).
• Carbonyl group's ability to react with electrophiles/nucleophiles (Nucleophilic addition, acyl substitution).
• Importance of carbonyl functional groups to the building block of organic molecules for biological function.

1,3-Dicarbonyls

• Contain multiple carbonyl groups.
• Reactivity arises from resonance.

Addition of amines to the carbonyl group

• Amines possess a lone pair on the Nitrogen atom.
• Amines can undergo nucleophilic addition to carbonyl groups.
• Imines (C=N bonds) are formed through reaction.

Grignard Reagents

• Formed from alkyl/aryl halides and magnesium.
• Organometallic compound (C-metal bond).
• High C-Mg bond polarity, carbon is nucleophilic.
• Used for C-C bond formation.

Hydride Reagents

• NaBH₄ and LiAlH₄ are used as H⁻ sources.
• Hydride charge is distributed over the anion.
• Boron and Aluminum are more electronegative than hydrogen.
• Negative charge predominantly on hydrogen atoms.
• Source of H⁻ for nucleophilic addition.

Nucleophilic Acyl Substitution

• Nucleophilic groups can add to carbonyl groups in carboxylic acid derivatives.
• Good leaving groups are required (e.g., Cl, OR).
• Leaving group departs during the reaction, form a temporary tetrahedral intermediate.
• Forming a new C=O bond results in the new substitution reaction.

Leaving Groups

• Substituents easily accepting negative charge.
• Stability of anion is crucial to determine its leaving capability.
• Leaving capabilities vary greatly depending on functional groups

Ester Hydrolysis

• OR groups are strongly electron-withdrawing.
• Oxygen is strong at donating electrons into C=O orbitals.
• Basic or acidic conditions speed up the hydrolysis of esters.
• Different mechanisms for basic and acidic ester hydrolysis (Nucleophilic addition by attacking nucleophiles and elimination of alkoxide).

Mechanism of Acid Ester Hydrolysis

• Protonation of ester, followed by nucleophilic attack by hydroxide.
• Elimination of alcohol by product.
• Regeneration of H+ (catalyst).

Esterification of Carboxylic Acids

• Transforming carboxylic acids into esters.
• Removal of water favors ester formation.

Amide versus Ester Hydrolysis

• Amides are less reactive than esters toward hydrolysis.
• Resonance stabilization plays a role in the differences in observed reactivity.