Pharmaceutical Organic Chemistry I PDF - Introduction to Organic Chemistry - Prof. Dr. Mostafa El-Miligy

Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Prof. Dr. Mostafa El-Miligy Professor of Pharmaceutical Chemistry Faculty of Pharmacy...

Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Prof. Dr. Mostafa El-Miligy Professor of Pharmaceutical Chemistry Faculty of Pharmacy Alexandria University 1 Syllabus of Pharmaceutical Organic Chemistry-1 (1) Introduction (2) Alkanes (3) Stereochemistry (4) Alkenes (5) Conjugated dienes (6) Alkynes (7) Alkyl halides (8) Aromaticity, Benzene and Arenes (9) Electrophilic Aromatic Substitution Reactions 2 Introduction to Organic Chemistry 1 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 3 YouTube Channel https://www.youtube.com/channel/UCNyMNr8kVH9Ze4XMsWDu-Og/featured 4 Introduction to Organic Chemistry 2 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 5 ❑Organic chemistry is the study of the compounds of carbon. ❑The compounds of carbon are the central substances of which all living things on this planet are made. 6 Introduction to Organic Chemistry 3 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Types of chemical bonds 1- Ionic Bond Na+ + Cl- NaCl Electrostatic attraction between positive and negative ions 7 Li + F Li+ + F− F− Li + F Li+ Li+ F− electron transfer He configuration Ne configuration ionic bond 8 Introduction to Organic Chemistry 4 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 2- Covalent Bond Sharing of electrons between 2 atoms occur through overlap of atomic orbitals to form either s or p bonds s spherical p dumbbell-shape 9 Types of overlap: 1) s and s overlap.... Bonding 1 1 H H H H Form s bond 10 Introduction to Organic Chemistry 5 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 2) s and p overlap.... H Cl 1 H (overlap with (form s bond) only one lobe) 11 3) p and p a) Head on overlap.... (one lobe only enters in overlap) Cl Cl (form s bond) b) sidewise overlap (electron cloud) nodal plane (electron cloud) (form p bond) A p bond is not formed unless a s bond is first formed 12 Introduction to Organic Chemistry 6 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 3- Coordination Bond (Semi-ionic Bond) Acceptor F has vacant orbital F F F B F F F F F B -B N : +N H H N H H Donor H H H has lone pair H of electrons H 13 4- Hydrogen Bond (H.B.) Types of Hydrogen Bonds: a- Intermolecular hydrogen bond − + − + O H O H H H H.B. is due to electrostatic attraction between + and − Association hydrogen bond leads to increase in boiling point Ethanol (C2H5OH, 780C), and diethyl ether (C2H5-O-C2H5, 320C) 14 Introduction to Organic Chemistry 7 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy b- Intramolecular hydrogen bond o-Nitrophenol p-Nitrophenol < M.P. Which one has higher melting point o-nitrophenol or p-nitrophenol and why? 15 β-diketone… 16 Introduction to Organic Chemistry 8 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Valency The number of electrons an atom must lose or gain to attain the nearest noble gas electronic configuration. 2px1 2py1 2pz 2s2 promotion 2px1 2py1 2pz1 Thus C is tetravalent 2s1 17 2px1 2py1 2pz1 sp3 sp3 sp3 sp3 sp3 2s1 2px1 2py1 2pz1 sp2 2py sp2 sp2 sp2 2s1 2px1 2py1 2pz1 sp 2py 2pz sp sp 2s1 This is called Hybridization Energy level of hybridized orbitals is between that of s and p orbitals 18 Introduction to Organic Chemistry 9 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Methane CH4 Overlap of four sp3 orbitals of C atom with four 1s orbitals of four H atoms H H sp3 C C H H 3 sp3 sp H H sp3 H H H Regular tetrahedral Bond angle 109o 28\ C tetrahedral hybridization H H H 19 1s 2s 2px 2py 2pz sp3 sp3 sp3 sp3 Promotey Hybridize x 109.5o z Methane: Carbon 20 Introduction to Organic Chemistry 10 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy H H Ethylene C C H H H H 2Py 2Py 2py 2py H 2 sp 2 H sp 2 SP SP2 C sp2 sp2 C C SP2 SP2 C SP2 SP2 sp2 sp2 H H H H H 2py 2py H H H H H C C C C C C H H H H H H Equilateral triangle trigonal Hybridization Bond angle 120oplanar 21 1s 2s 2px 2py 2pz sp2 sp2 sp2 Promoted Hybridized Trigonal 120o Planar 2s + 2px + 2pz 22 Introduction to Organic Chemistry 11 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Acetylene H C C H 2py 2pz 2py 2pz H sp C sp sp C sp H 2py 2py 2pz 2pz H C C H H C C H HC CH linear Bond angle 180o planar 23 1s 2s 2px 2py 2pz sp sp Promoted Hybridized Linear 2s + 2px 24 Introduction to Organic Chemistry 12 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Effect of hybridization on bond length and acidity Electrons in S orbitals are strongly attached to the nucleus %S character bond length %S character acidity 25 Effect of hybridization on bond length and acidity sp3 C sp2 C sp C Bond type example CH3-CH3 CH2=CH2 CH CH % S Character 25 33.3 50 Acidity Non Less Most acidic acidic acidic 26 Introduction to Organic Chemistry 13 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Electronegativity Is the ability of an atom to attract bonded electrons closer to itself H3C Cl + − According to electronegativity: F > O > N,Cl > Br > C,S > H 4.0 3.5 3.0 2.82 2.5 2.25 27 Dipole moment − + H H F H nonpolar compound Dipole moment = 0 polar compound posses a dipole moment Direction is indicated by an arrow directed to the negative end e.g. Carbon dioxide CO2 is polar or non-polar ?? e.g. Water H2O is polar or non-polar ?? 28 Introduction to Organic Chemistry 14 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 29 Factors Affecting Electron Availability at an Atom 1- Inductive effect 2- Resonance 30 Introduction to Organic Chemistry 15 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 1- Inductive effect: H2 H2 − CH3 C C Cl + + + - I (out of Carbon) +I (to Carbon) electron withdrawing gp electron donating gp e.g. NO2,CN, SO3H,CHO, COR e.g.Alkyl groups F,Cl,Br,I 31 2- Resonance + - C O C O 2 canonical structures C C C O C C C O C C C O + - + - conjugated system 32 Introduction to Organic Chemistry 16 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 33 O O C H C R O R O O C R O number of canonical structures stability 34 Introduction to Organic Chemistry 17 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Inductive effect Resonance occur only in occur in unsaturated and saturated systems conjugated systems It is the tendency of delocalization of p es or an atom or group of lone pair in a planar system atoms to attract or (parallel p orbitals) release electrons transmission effect continue as long as fades by increasing conjugation extends distance 35 Breaking of a covalent bond a) homolytic fission R Y R. + Y. Free radical formed by the effect of heat or light b) heterolytic fission + − R+ + Y- R Y Carbocation − + R MgX R- + MgX+ Carbanion 36 Introduction to Organic Chemistry 18 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy Reaction intermediates Carbocations C+ Carbanions C- Electron defficient center Electron rich center Stabilized by EDG Stabilized by EwG Stabilized by +I and Stabilized by –I and resonance resonance Called electrophile E+ Called nucleophile Nu- React with Nu- React with E+ 37 Arrows in Organic Chemistry Chemical Reaction Arrow Resonance Arrow Equilibrium Arrow Electron Arrows 38 Introduction to Organic Chemistry 19 Pharmaceutical Organic Chemistry I Prof. Dr. Mostafa El-Miligy 39 Introduction to Organic Chemistry 20