Pharmaceutical Organic Chemistry 1 Introduction PDF

Pharmaceutical Organic Chemistry 1 (Introduction) By Dr. Aya Almatary  Electronegativity (EN) is the affinity for electrons or intrinsic ability of an atom to attract the shared electrons in a covalent bond. Differences in EN...

Pharmaceutical Organic Chemistry 1 (Introduction) By Dr. Aya Almatary  Electronegativity (EN) is the affinity for electrons or intrinsic ability of an atom to attract the shared electrons in a covalent bond. Differences in EN produce bond polarity. F is most electronegative (EN = 4.0) Cs is least (EN = 0.7) Metals on left side of periodic table attract electrons weakly, having lower EN Halogens and other reactive non-metals on right side of periodic table attract electrons strongly, having higher EN F > O > Cl > N ~ Br > I ❑ EN of C = 2.5 2  Effect of Electronegativity on Bond Polarity The difference in electronegativities determines the type of bond as follows: ❑ Nonpolar Covalent Bonds: difference in EN of atoms 2 3  Polar Covalent Bonds When the bonding electrons are attracted towards the more electronegative atom, it will acquire a partial -ve charge, δ-, while the other atom will acquire a partial +ve charge, δ+. 4  Practice Indicate whether the given bonds are ionic (I), polar covalent bond or non-polar covalent bond. 1.C–Li 2.N–H 3.Na-Br 4.S–O 5.C-H 5  Electrostatic Potential Maps ❑ Electrostatic potential maps show calculated charge distributions. ❑ Colors indicate electron-rich (red) and electron-poor (blue) regions. Arrows indicate direction of bond polarity. 6  Dipole moment (μ) Dipole moment (μ) Measures the net polarity of the molecule (or it is the vector sum of all the individual bond polarities and lone-pair contributions (unit is Debye D). 7 Dipole moment (μ) 8  Applications on dipole moment 1- Differentiation of the three di-substituted products of benzene: μ = 1.6 D μ ˃ 1.6 D μ =0 D 2- Assignment of the configuration of the geometrical isomers: eg. C2H2Cl2 (cis, trans) 9  Absence of Dipole Moments In symmetric molecules, dipole moments within the molecule are in opposite directions. The effects of the local dipoles cancel each other. 10  Electron displacement factors factor that influences the relative availability of electrons (electron density) in particular bond or at particular atoms in a compound Inductive effect Mesomeric effect Hyperconjugation 11  Inductive Effect (I) It is shifting of electrons in a bond in response to EN of nearby atoms. It is the effect due to the difference of electronegativity between the atoms bonded by a covalent bond, also known as Bond Polarization 12  Inductive Effect (I) The inductive effect decreases rapidly as the distance from the source increases. The inductive effect may be ignored after C2. Functional groups can be classified as electron-withdrawing (-I) or electron-donating (+I) groups relative to hydrogen. 13  Inductive Effect and the Behavior of Organic Compounds 1- SN2 displacement reaction 2- Stability of carbocations in solution obeys the order 3ry > 2ry > 1ry 14  Resonance Effect (Mesomeric Effect) Resonance is an effect related to unsaturated compounds especially in conjugated systems (?) in which delocalization of electrons takes place via their p orbitals (Pi bond). Only electrons move in a resonance structure e.g 1: Carbonate ion, CO32- One resonance contributor is converted to another by the use of curved arrows which show the movement of electrons.15  Resonance and Stability of Benzene In benzene, there is a special stability associated with aromatic character and this stability is due to resonance. Delocalized π Molecular Orbitals in benzene 16  Resonance and Stability of Carbocations Resonance is also used to explain the stabilization of allyl and benzyl carbocation. The presence of a vacant pAO allows for resonance interaction with the p MO’s leading to dispersion of the +ve charge over the atoms at opposite ends of the conjugated system. The order of stability of carbocations: Benzylic ~ 3ry > allylic ~ 2ry > 1ry > methyl 17  Hyperconjugation ❑ Hyperconjugation is the stabilizing interaction that results from the interaction of electrons in a σ-bond (usually C-H or C-C) with an adjacent empty or partially filled p-orbital or a π-orbital to give an extended molecular orbital that increases the stability of the system. 18 Hyperconjugation 19 THANKS! Any questions? You can find me at ✘ [email protected] ✘ Office hours: Saturday, 12-2 p.m. At p103 20