AldehydesKetones 9

Page 1: Introduction

  • Course Title: PHAR201 Towards unbounded Carbonyl Compounds

  • Focus on Aldehydes & Ketones

  • Instructor: Dr. Mohamed Salah (M.Salah@ngu.edu.eg)

  • Institution: School of Pharmacy, NGU

Page 2: Learning Outcomes

  • Describe chemical characteristics and reactivity of functional groups.

  • Understand stereochemistry of drugs and its relation to drug activity and toxicity.

  • Explain the importance of structure and bonding in drug molecules.

  • Discuss effects on molecular shape, physical properties, chemical properties, and interactions with other molecules.

  • Evaluate their pharmaceutical use.

Page 3: Overview

  1. Introduction to carbonyl compounds

  2. Nature of carbonyl group

  3. Aldehydes and Ketones

    • A. Nomenclature

    • B. Reactivity

      • Nucleophilic Addition Reactions

Page 4: Carbonyl Compounds - Introduction

  1. Pronunciation: car-bo-neel

  2. Ubiquity of carbonyl compounds in nature (e.g. citric acid, acetaminophen).

  3. Presentation as part of many functional groups.

Page 5: Types of Carbonyl Compounds

  • A. Aldehydes and Ketones (1 Lecture)

  • B. Carboxylic Acids and their Derivatives (2 Lectures)

Page 6: Nature of the Carbonyl Group

  1. Carbon–oxygen double bond of carbonyl is analogous to carbon–carbon double bond of alkenes.

Page 7: Structure of the Carbonyl Group

  1. sp2 hybridization of carbon and oxygen results in a planar structure.

Page 8: Polarization of the Carbonyl Group

  1. Carbon–oxygen double bond is strongly polarized due to oxygen's high electronegativity.

    • Electrophilic (Lewis acidic) sites and nucleophilic (Lewis basic) sites are established.

Page 9: Hydrogen Bonding Effects

  1. Hydrogen bonding influences boiling points and solubility of aldehydes and ketones.

    • Example: Pentanal (69°C boiling point) vs. Pentan-1-ol (102°C boiling point).

Page 10: Naming Aldehydes

  1. The parent chain must contain the –CHO group (Carbon 1 is the carbonyl carbon).

  2. Aldehydes are named by replacing the ‘-e’ in the alkane name with ‘-al’.

Page 11: Common Names of Simple Aldehydes

  • HCHO: Formaldehyde

  • CH3CHO: Acetaldehyde

  • CHO: Benzaldehyde

Page 12: Naming Ketones

  1. Longest chain containing the ketone group is the parent chain.

  2. Numbering starts from the end closest to the carbonyl carbon.

  3. Naming involves replacing ‘-e’ in the alkane name with ‘-one’.

Page 13: Common Names of Simple Ketones

  • CH3C(CH3)2: Acetone

  • C6H5C(O)R: Acetophenone

  • C6H5C(O)C6H5: Benzophenone

Page 14: Alpha Proton Acidity

  1. Definition of α Proton (adjacent to carbonyl).

  2. Weakly acidic due to resonance stabilization of the conjugate base.

Page 15: Effect of Multiple Carbonyls

  1. Acidity of α Protons is increased with multiple carbonyl groups.

    • Example: penta-2,4-dione has a pKa of 9.

Page 16: Nucleophilic Addition Reactions

  • Introduction to the concept of nucleophilic addition reactions involving carbonyl compounds.

Page 17: Mechanism of Nucleophilic Addition

  1. Nucleophile adds to electrophilic carbon of C=O group.

  2. Rehybridization of carbon from sp2 to sp3.

  3. Movement of electron pair from C=O bond to oxygen.

  4. Formation of tetrahedral alkoxide ion intermediate.

  5. Protonation of the alkoxide ion.

Page 18: Aldehydes vs Ketones

  • Aldehydes are generally more reactive than ketones for two reasons:

    1. Steric hindrance - fewer steric hindrances in aldehydes.

    2. Electronic factors - Aldehydes show greater polarization in carbonyl than ketones.

Page 19: Aldehydes vs Ketones - Sterics

  1. One large substituent in aldehydes allows easier nucleophile approach as compared to two large substituents in ketones.

Page 20: Aldehydes vs Ketones - Electronics

  1. Greater polarization in aldehyde carbonyls compared to ketones contributes to their reactivity.

Page 21: Reaction with Alcohols

  1. Aldehydes and ketones react with alcohols to create hemiacetals or hemiketals.

Page 22: Nucleophilic Addition-Elimination Reactions

  1. Primary amines react with aldehydes/ketones to yield imines (Schiff bases).

Page 23: Reaction Mechanism with Amines

  1. Addition of amine to carbonyl forms a dipolar tetrahedral intermediate.

  2. Proton transfer from nitrogen to oxygen yields an amino alcohol intermediate.

  3. Dehydration forms an imine and water as final products.

Page 24: Example of Amines Reaction

  1. Example: The amino acid alanine reacts with pyridoxal phosphate to yield an imine.

Page 28: References

  1. McMurry, J. Organic Chemistry, 9th edition, 2019.

  2. Sarker, S. D. and Nahar, L. Chemistry for Pharmacy Students.

Page 29: Conclusion

  • Encouragement towards unbounded thinking.

  • Reminder of NGU School of Pharmacy thanks.