Pharmaceutical Organic Chemistry-I (Pharm D) - POC 101 2020/2021 PDF

Pharmaceutical Organic Chemistry-I (Pharm D) - POC 101 2020/2021 By Assoc. Prof. Dr. Phoebe F. Lamie Course Content: Introduction Saturated hydrocarbons (alkanes & cycloalkane) and their stereochemistry Unsaturated hydrocarbons (alkenes &...

Pharmaceutical Organic Chemistry-I (Pharm D) - POC 101 2020/2021 By Assoc. Prof. Dr. Phoebe F. Lamie Course Content: Introduction Saturated hydrocarbons (alkanes & cycloalkane) and their stereochemistry Unsaturated hydrocarbons (alkenes & alkynes) Halogenated hydrocarbons (alkyl halides, alkenyl halides & organometalic compounds) Aromatic organic chemistry (Benzene, aromaticity, benzene derivatives & arenes)  INTRODUCTION Organic Chemistry : is the study of Carbon compounds. Hydrocarbons: are compounds containing only C & H. Functional group is the reactive site of the organic molecule. (e.g. CH3CH2OH, CH3COOH, CH3CH=CH2,.......etc). Functional group priority (in IUPAC Naming): rearrangement order of funcyional groups, -COOH, -COX, -CONH2, -CHO, -CO-, -OH, -NH2, = / ≡ , -X, -R.  Representation of the Organic Structure 1- Dash structural formula: 2- Condensed structural formula: e.g.: Diethyl ether: 3- Bond-line formula:  Electronegativity (EN) it is the tendency or the ability of an atom to attract electrons. EN increases in the same period with the increase in the atomic number while decrease in the same group increase in the atomic number. H (2.2) Li (1.0) Be (1.6) B (2.0) C (2.6) N (3.0) O (3.4) F (4.0) Na (0.9) Cl (3.2) K (0.8) Br (3.0) I (2.7)  Types of Chemical Bonds According to the difference in EN between the bonded atoms, the chemical bonds are classified into: 1) Ionic Bonds: [ΔEN > 2 ] e.g. Sodium Chloride: Na+Cl- (ΔEN = 2.3) 2) Covalent Polar Bonds: [2 > ΔEN > 0.5] e.g. Methyl Chloride: H3C+δ-Cl-δ (ΔEN = 0.6). Methyl Lithium: H3C-δ-Li+δ (ΔEN = 1.6). 3) Covalent Non-Polar Bonds: [ΔEN = 0 to 0.5] e.g. Bromine: Br-Br, Ethane: H3C-CH3 (ΔEN = 0).  Attractive forces between atoms in Organic molecules 1) Dipole-Dipole interactions: e.g. Methyl Chloride: H3C+δ-Cl-δ------- H3C+δ-Cl-δ------- H3C+δ-Cl-δ 2) Hydrogen Bonds: 3) London Forces: e.g. Halogens (Br+δ-Br-δ) The order of polarizability I2 (solid)> Br2 (liquid)> Cl2 (liquid)> F2(gas).  Electron effects of Substituent on Organic molecules Inductive effect (I effect) Mesomeric effect (M effect) It can be occurred Only by substituents in 1 It can be occurred by substituents in All molecules. Unsaturated Conjugated molecules. It is electron delocalization via π bonds. 2 It is electron displacement via ϭ bonds. 3 It undergoes permanent polarization in molecules. It undergoes permanent polarization in molecules. It decreases with the increase of distance from It stays stable effect with the increase of distance 4 substituent. from substituent O H 2C C C C CH H H H SSS+ SS+ S+ S- 5 H3C CH2 CH2 Cl O H 2C C C C CH H H H Substituent has (-M) effect when it has functional gp Substituent has (-I) effect when it has more EN than C. e.g. -C=O, C≡N, or N=O, conjugated with the e.g. F, Cl, Br, I, O, or N. 6 molecule. And it means that the e' displacement is toward the And it means that the e' delocalization is toward the Substituent. Substituent. Substituent has (+M) effect when it has functional gp Substituent has (+I) effect when has less EN than C. e.g. -OH, OR, NH2 or NHR, conjugated with the e.g. Li, Na, Mg, Cu, Cd or R (alkyl) groups. 7 molecule. And it means that the e' displacement is away from And it means that the e' delocalization is away from the Substituent. the Substituent Substituents having –I and/ or –M are called electron withdrawing groups while Substituents having +I and/ 8 or +M are called electron donating groups  Types of Bond Cleavage 1) Heterolytic Cleavage: 2) Homolytic Cleavage: Carbons containing intermediadtes Carbocation Carbanion 1 It positively charged species It negatively charged species 3o Carbocation is more stable than 2o 3o Carbanion is less stable than 2o than 1o than 1o cabocation as +I effect of the alkyl cabanion as +I effect of the alkyl (R) group 2 (R) group stabilizes the carboction. destabilizes the carboction. 3o > 2o > 1o > CH3 carbocation 3o < 2o < 1o < CH3 carbanion + I effect CH3 + I effect CH3 H3C C H 3C C 3 CH3 CH3 Stable Carbocation Unstable Carbanion 4 The stability of Carbon free radicals are the same as that of carbocation stability. Allyl Carbocation, Carbanion and Free radical is the most stable one due to Resonance 5 stability. H2C CH CH2 H2C HC CH2  Types of Chemical Reagents Electrophile E+ Nucleophile Nu- It is an e' seeking (loving) It is seeking for low e' density 1 species center E+ may be positively charged Nu- may be negatively charged 2 atom or group e.g. H+, X+, atom or group e.g. OH-, X-, H-, NO2+, …..etc. CN- …..etc. E+ may be neutral molecule Nu- may be neutral molecule when it contains vacant when it contains unshared pair 3 orbital e.g. AlCl3, FeCl3. of electrons e.g. H2O, ROH, NH3, Also, Carbenes and Free RNH2. radicals are considered as E+  Types of Chemical Reactions 1) Substitution Reactions: A) Nucleophilic Substitution Reactions (SN): B) Electrophilic Substitution Reactions (SE): C) Free Radical Substitution Reactions: 2) Addition Reactions: A) Nucleophilic Addition Reactions: B) Electrophilic Addition Reactions: C) Free Radical Addition Reactions: 3) Elemination Reactions: A) α- Elemination Reactions: B) β- Elemination Reactions: C) γ- Elemination Reactions: