Pharmaceutical Organic Chemistry 1st Session 2024-2025 Lecture Notes PDF

Welcome to the 3rd semester of Pharmaceutical Organic Chemistry 1st session 2024-2025 GENERAL PHARM-D3 INSTRUCTORS: PROF. DR/ BAHAA G.M. YOUSSIF M.SC./ SAMIA MOUSTAFF M.SC./ FATMA ELZAHRAA ALI PH/ AMIRA M AHMOUD MOHAMED PH/ HESHAM T. RAMADAN HEAD O...

Welcome to the 3rd semester of Pharmaceutical Organic Chemistry 1st session 2024-2025 GENERAL PHARM-D3 INSTRUCTORS: PROF. DR/ BAHAA G.M. YOUSSIF M.SC./ SAMIA MOUSTAFF M.SC./ FATMA ELZAHRAA ALI PH/ AMIRA M AHMOUD MOHAMED PH/ HESHAM T. RAMADAN HEAD OF DEPARTMENT PROF. DR/ MOSTAFA AHMED HUSSEIN week Subject Demonstration (No. Points ( 28/9/2024 Writing reaction mechanism & TLC Theoretical (1) 5/10/2024 Lab safety, Synthesis of Isatin + Tutorial Theoretical (1) 12/10/2024 Synthesis of Isatin Practical (3) 19/10/2024 Synthesis of coumarin + Tutorial Theoretical (1) 26/10/2024 Synthesis of Coumarin + Tutorial Practical (3) 2/11/2024 Electrostatic potential map Theoretical (1) 9/11/2024 Electrostatic potential map Practical (3) MOE lab. 16/11/2024 Benzotriazole synthesis + Tutorial Theoretical (1) 23/11/2024 Benzotriazole synthesis Practical (3) 30/11/2024 Synthesis of Benzimidazole and quinoxaline + Tutorial Theoretical (1) 7/12/2024 Synthesis of Benzimidazole / quinoxaline + Tutorial Practical (3) 14/12/2024 Sheet 15 Item Mark Attendance 6 Practical work 15 Sheet 15 Report 4 Laboratory safety Safety First  Basic regulations which must be followed:  Most organic substances are hazardous to health; so, avoid breathing and skin contact as much as possible (wear gloves).  Never taste any solid or liquid chemicals whatever the reason. Never eat, drink or chew gum while working in the lab. Never wear contact lenses in the lab as it may adsorb chemicals Confine long hair when working in the laboratory; Since it may come in contact with chemicals.  If chemicals come into contact with your clothes, skin or eyes; wash immediately with aplenty of water for 15 minutes and consult your instructor.  Know where and how to use safety showers and fire extinguishers.   Working with toxic, lachrymatory or irritant chemicals must be conducted under the fume hoods. If inhale vapors:  Consult your instructor to leave contaminated area and go outside into fresh air.   Disposal of different materials 1- Throw all solids to be discarded into the waste paper basket. 2- Never throw filter paper, broken glass or any insoluble chemicals into the sink 3-Organic liquids must be collected in a waste disposal bottles. Writing Reaction Mechanism Types of arrows in organic chemistry 1. The forward arrow: or the Reaction arrow indicate complete transformation of the reactant to product (Irreversible) Types of arrows in organic chemistry 2. The Equilibrium arrow: indicate the presences of equilibrium between two forms of structure or reversibility of the chemical reaction. Types of arrows in organic chemistry 2. The Equilibrium arrow also can be used to show which form of structure is predominant. Types of arrows in organic chemistry 3. Resonance arrow: it’s a double-headed arrow shows two (or more) species that are resonance structures(they differ in the arrangements of their electrons) of each other. Types of arrows in organic chemistry 4. The Curved Arrow: this arrow is to show the movement of an electron pair. Types of arrows in organic chemistry 5. Single headed curved Arrow (fish hock): Shows the movement of a single electron. Mechanisms and Arrow Pushing All ionic mechanisms are simply combinations of four steps. 1. Nucleophilic Attack. 2. Loss of a Leaving Group. 3. Proton Transfers. 4. Rearrangements. 1-Nucleophilic Attack Nucleophiles: an electron-rich atom that is capable of donating a pair of electrons. the terms “nucleophile” and “Lewis base” are synonymous. Ethoxide Ethanol 1-Nucleophilic Attack Electrophiles: an electron-deficient atom that is capable of accepting a pair of electrons. The terms “electrophile” and “Lewis acid” are synonymous.  1-Nucleophilic Attack The first pattern is nucleophilic attack, characterized by a nucleophile attacking an electrophile.  1-Nucleophilic Attack The first pattern is nucleophilic attack, characterized by a nucleophile attacking an electrophile. electrophile nucleophile 2- Loss of a Leaving Group 3- Proton Transfers 4- Rearrangements. 4- Rearrangements. There are two common ways in which carbocation rearrangements are accomplished: via either a hydride shift or a methyl shift. Problems For each of the following cases, read the curved arrows and identify which arrow-pushing pattern is utilized. Combining the Patterns of Arrow Pushing All ionic mechanisms, regardless of how complex, are just different combinations of the four characteristic patterns. For example, SN1 OH Br HBr Combining the Patterns of Arrow Pushing Mechanism of SN1 Loss of leaving group Nucleophilic attack Rearrangement Proton transfer Problems Problems Read the curved arrows and identify the sequence of arrow pushing patterns: Proton transfer Loss of leaving group Proton transfer Nucleophilic attack Problems Mark the wrong arrows Problems Read the curved arrows and identify the sequence of arrow–pushing patterns: Proton transfer Nucleophilic attack Proton transfer Problems Draw the curved arrows that accomplish each of the following transformations:  THIN-LAYER CHROMATOGRAPHY ‘TLC’  THIN-LAYER CHROMATOGRAPHY This technique is used to differentiate between compounds according to their polarity. We dissolve some crystals of each comp. in a suitable solvent then we make a spot for each compound. A suitable solvent system is chosen for development.  Selection of the solvent system. If the behavior of the substance under investigation is unknown, the most satisfactory developing solvent must be tested by preliminary trial runs It is convenient to set up a series of solvent systems of increasing polarity. For example, hexane, toluene, carbon tetrachloride, dichloromethane, diethyl ether, ethyl acetate, acetone, methanol.  Selection of the solvent system Solvents which cause all the components to remain near to the spot origin or to move near to the solvent front are clearly unsatisfactory. If it is seen that no single solvent gives a satisfactory chromatogram, with well-spaced compact spots. It is necessary to examine the effect of using mixtures of solvents to provide systems having a range of intermediate polarity. For example, mixtures of toluene and methanol, or hexane and ethyl acetate, are often suitable. Selection of the solvent system  Development of plates Individual plates are conveniently developed in a cylindrical glass jar Insert the plate with the origins spot towards the bottom of the jar. The time required to complete this development varies greatly with the composition of the solvent (mobile phase) and the nature of the adsorbent )stationary phase which holds molecules (spots) at its surface. After removal, the plate is dried suitably depending upon the volatility and toxicity of the solvent system.  For example, dry the plate in the fume cupboard (if necessary) with a warm-air blower or dry in a temperature-controlled oven, etc.  Location of spots Viewing the plate under an ultraviolet lamp will reveal u.v. fluorescent compounds the positions of which must of course be marked with the scriber on the surface of the adsorbent.  Retardation factor “RF” When the experimental conditions are reproducible the movement of any substance relative to the solvent front in a given system is constant and characteristic of the substance. The constant is the RF value and is defined as: ratio of the distance traveled by the center of a spot to the distance traveled by the solvent front.  Tlc can be used to monitor reactions At the beginning of the reaction S1 : start 1 S1 RX S2 S1 RX S2 S2 : start 2 RX : reaction mixture  Tlc can be used to monitor reactions At the End of the reaction New spot can appear above, below or S1 : start 1 S1 RX S2 S1 RX S2 between the spots of S2 : start 2 the starts RX : reaction mixture Normal phase TLC Less polar  Polar stationary phase (silica gel) more polar  Non polar mobile phase  Report “4 Marks” Prepare report on the selected reaction on word Items needed : 1-general equation 2-needed reagents 3-procedure 4-mechanism 5- biological activity 6-representative drugs 7-spectral data 8-Physical data ‘M.P., Rf ’ 9-Electrostatic potential map. 10-Yield calculations 11-References All structures and mechanisms must be drawn using chem draw M.P. must be mentioned as estimated and reported 48