Pharmaceutical Organic Chemistry 1: Electronegativity

Pharmaceutical Organic Chemistry 1 (Introduction)

• This is an introductory course in Pharmaceutical Organic Chemistry.
• Key formulas include E=mc² and V2.
• H₂O is a molecule mentioned.

Electronegativity

• Electronegativity (EN) is the affinity of an atom for electrons in a covalent bond.
• Differences in electronegativity create bond polarity.
• Fluorine (F) has the highest electronegativity (EN = 4.0).
• Cesium (Cs) has the lowest electronegativity (EN = 0.7).
• Metals on the left side of the periodic table have lower electronegativity and attract electrons weakly.
• Halogens and other reactive non-metals on the right side of the periodic table have high electronegativity and attract electrons strongly.
• EN of Carbon (C) = 2.5
• Electronegativity values are given for various elements in the periodic table.

Effect of Electronegativity on Bond Polarity

• Nonpolar covalent bonds form when the difference in electronegativity between atoms is less than 0.5. Examples include C-H bonds.
• Polar covalent bonds form when the difference in electronegativity is between 0.5 and 2. Examples include C-O, C-X bonds where X is a highly electronegative element.
• Ionic bonds form when the difference in electronegativity is greater than 2.

Polar Covalent Bonds

• Bonding electrons are attracted to the more electronegative atom, creating a partial negative charge (δ-) on that atom and a partial positive charge (δ+) on the other atom.
• Examples of polar covalent bonds include C-F, B-F, and C-O-H

Practice Problems

• Determine if bonds are ionic, polar covalent, or nonpolar covalent. Examples include C-Li, N-H, Na-Br, S-O, and C-H bonds.

Electrostatic Potential Maps

• Electrostatic potential maps show charge distributions.
• Red areas indicate electron-rich regions.
• Blue areas indicate electron-poor regions.
• Arrows indicate bond polarity direction.
• Examples presented include Methanol and Methyllithium.

Dipole Moment (μ)

• Dipole moment measures the net polarity of a molecule.
• It's calculated as the vector sum of individual bond polarities and lone-pair contributions.
• Units are Debye (D).
• Values are given for various molecules like N-H, and F-F.

Applications of Dipole Moments

• Differentiating di-substituted benzene products (with different μ values).
• Assigning configurations of geometrical isomers like C₂H₂Cl₂ (cis- and trans-dichloroethenes).

Absence of Dipole Moments

• In symmetric molecules, dipole moments cancel each other out because the opposing dipoles in the molecule are equal and in opposite directions. Examples include CO₂, CH₄, CCl₄, Ethane, and Benzene.

Electron Displacement Factors

• Factors influencing electron availability (electron density) in bonds or atoms.
• Three factors are discussed: inductive effect, mesomeric effect, and hyperconjugation.

Inductive Effect

• Electron shift in a bond due to electronegativity differences of neighboring atoms.
• This results in a bond polarization effect—one end of the bond has a partial positive or negative charge depending on the surrounding atoms' electronegativity.
• The inductive effect weakens with increasing distance from the source.
• Inductive effects from atoms beyond C2 are often ignored in calculations.

Mesomeric Effect (Resonance)

• Delocalization of electrons in conjugated systems, especially in π bonds.
• Carbonate ion (CO₃²⁻) is used as an example.

Resonance and Stability of Benzene

• Benzene exhibits enhanced stability due to resonance, a feature of its aromatic character.

Resonance and Stability of Carbocations

• Resonance enhances the stability of carbocations like allyl and benzyl carbocations.
• The order of increasing carbocation stability is generally benzylic 3° > allylic 2° > 1° > methyl.

Hyperconjugation

• Stabilizing interaction of σ bonding electrons (typically C-H or C-C) with empty or partially filled p or π orbitals.
• Results in extended molecular orbitals, increasing the stability of the molecule.
• Illustrated in propene.

Contact Information

• Contact information for the instructor (Dr. Aya Almatary) is provided for further questions.