Basic Pharmaceutical Organic Chemistry Lecture Notes (PDF)

‫بسم هللا الرحمن الرحيم‬ ‫◼‬ ‫‪1‬‬  lco e m W e we e lcom m c o e e l w ◼ 2  ‫ جامعة مصر للعلوم والتكنولوجيا‬- ‫رؤية كلية الصيدلة‬...

‫بسم هللا الرحمن الرحيم‬ ‫◼‬ ‫‪1‬‬  lco e m W e we e lcom m c o e e l w ◼ 2  ‫ جامعة مصر للعلوم والتكنولوجيا‬- ‫رؤية كلية الصيدلة‬ College Vision ً ‫تسعى الكلية أن تكون مؤسسة متميزة دوليا فى مجال الصيدلة من أجل تطويرمهنة الصيدلة‬ ً.2030‫وتحقيقا لرؤية مصر‬ The college seeks to be an internationally distinguished institution in the field of pharmacy in order to develop the pharmacy profession and to achieve Egypt’s 2030 vision. ◼ 3  College Mission ‫تهدف كلية الصيدلة جامعة مصرللعلوم والتكنولوجيا بإعداد صيادلة متمسكين بقيم وأخالقيات مهنة الصيدلة قادرين على‬ ً ً.‫املنافسة محليا و إقليميا من خالل برامج أكاديمية متطورة تلبى احتياجات سوق العمل باستخدام تقنيات تكنولوجية حديثة‬ ‫كما تحرص الكلية على دعم البحث العلمى التطبيقى فى مجاالت صناعة الدواء وصحة املريض وتقديم خدمات مجتمعية وتحقيق‬ ‫الشراكة الفعاله مع املجتمع الداخلى والخارجى من أجل التنمية املستدامة‬ The College of Pharmacy- Misr University for Science and Technology aims to prepare pharmacists who adhere to the values and ethics of the pharmacy profession and who are able to compete locally and regionally through advanced academic programs that meet the needs of the labor market using modern technological techniques. The college is also keen to support applied scientific research in the fields of drug industry, patient health, provide community services, and achieve effective partnership with the internal and external community for sustainable development. ◼ 4  Basic Pharmaceutical Organic Chemistry ◼ 5  Basic Information Programme(s) on which the course is Bachelor of Pharmacy (PharmD) given: Department responsible for offering the Pharmaceutical Organic Chemistry course: Department responsible for teaching the Pharmaceutical Organic Chemistry course: Academic year: First year-first semester Course title and code: Basic Pharmaceutical Organic Chemistry code: POC 101 (3 credit hours) Lecture:2 ( 2) , Practical : 2 (1) ◼ 6 Overall Aims of Course The aim of the course is to ensure that the graduated pharmacist achieved the competencies of integration of the knowledge and skills obtained from studying this course with advanced courses to ensure that students understand the fundamental principles of chemistry of aliphatic organic compounds and their mechanisms of the reactions. ◼ 7 Competencies, key elements and learning outcomes of the course (1-10) 1.1. Integrate knowledge from basic and applied pharmaceutical and clinical sciences to standardize materials, formulate and manufacture products, and deliver population and patient-centered care This competency will be achieved through the following keyelements: 1.1.1.Demonstrate understanding of pharmaceutical, biomedical, social, behavioral pharmacology, administrative, and clinical sciences. Learning Outcomes By the end of the course the student should be able to demonstrate knowledge and understanding of 1- The basic of aliphatic organic reactions. 2- The mechanism of aliphatic organic reactions. 3. The basic concepts of isomerism and geometrical isomerism 4. The principles of identification of organic compounds. ◼ 8 1.1.3. Integrate knowledge from fundamental sciences to handle, identify, extract, design, prepare, analyze, and assure quality of synthetic/natural pharmaceutical materials/products. Learning Outcomes 5. Select methods for identification of organic compounds from both physical and chemical reactions (reactions of functional groups). 6. Solve the chemical reaction problems of aliphatic compounds 2.2. Standardize pharmaceutical materials, formulate and manufacture pharmaceutical products, and participate in systems for dispensing, storage, and distribution of medicines 2.2.1. Isolate, design, identify, synthesize, purify, analyze, and standardize synthetic/natural pharmaceutical materials. Learning Outcomes: 7. Apply suitable methods to identify different classes of aliphatic organic compounds ◼ 9 ◼ 10  No. of No. of credit Total no. Lecture credit Week no. hours Practical of credit hours hours Introduction to organic chemistry, type of chemical Introduction, safety& name of glassware &lab. tools 1 2 2(1) 3 bonds and their uses Hybridization and their types & representation of Physical Character of organic compounds 2 2 2(1) 3 organic compounds, (Condition, Colour, Odour& Solubility). Type of isomerism, and the principle of nomenclature Chemical Character of organic compounds (Soda 3 2 2(1) 3 and resonance theory lime, NaOH, FeCl3& Conc. H2SO4) Classification of organic compounds. Saturated hydrocarbons (Alkanes & Cycloalkanes). Identification of alcohols. 4 2 2(1) 3 Nomenclature, isomerism, preparation and reactions Nomenclature of Alkenes and cycloalkenes &, 5 2 Identification of Aldehydes. 2(1) 3 geometrical isomerism (Z- or E- configuration) 6 Preparations & reactions of Alkenes and cycloalkenes.) 2 Identification of ketones 2(1) 3 Nomenclature, isomerism, preparations & reactions of 7 2 Identification of Liquid Aliphatic Carboxylic Acids. 2(1) 3 Alkynes. Alkyl halides. Nomenclature, isomerism, preparations 8 2 Identification of Solid Aliphatic Carboxylic Acids. 2(1) 3 and reactions Alcohols & Ethers. Nomenclature, Identification of Salts of aliphatic carboxylic 9 2 2(1) 3 isomerism, prepartions and reactions Acids.(Amm., K+, Na+…..) Nomenclature, isomerism, preparations & reactions of 10 2 Identification of carbamide ( Urea) 2(1) 3 aliphatic aldehydes & Ketones. Nomenclature, isomerism, preparations & reactions of Revision (General Scheme for Solid & Liquid 11 2 2(1) 3 Aliphatic carboxylic acids. Unknowns) Nomenclature ,isomerism ,preparations & reactions of Revision (General Scheme for Solid & Liquid 12 2 2(1) 3 Derivatives of aliphatic of carboxylic acids. Unknowns) Nomenclature, isomerism, preparations & reactions of 13 2 Practical final exam 2(1) 3 Aliphatic amines 14 Carbamide & Revision 2 Practical final exam 2(1) 3 11 Total 28 28(14) 42  To The Students ◼ Keep up with your work from day to day never let yourself get behind. ◼ Study material in small units and be sure that you understand each new section before you go on to the next. ◼ Work of the in-chapter and assigned problems. Do not refer to the answer of problems, before you have finished them or making a real effort to solve it. ◼ Write when you study; writ the reaction, mechanisms, structures and so on, over and over again. Do not study through the eyes or by highlighting material in text, or by referring to flash cards. 12 Introduction 13  Life is Organic Chemistry ◼ Organic molecules are at the heart of life of both the existence of life on earth and the possibility of life elsewhere 14  Importance of organic compounds ◼ There is no art, science or industry where knowledge of organic chemistry is not applied. The importance of organic chemistry is briefly outlined below. 1. Study of life processes they posses exclusive biological roles 2. In daily life: we find ourselves in strange panorama of things that are connected with organic chemistry. 3. In industry: Knowledge of organic chemistry is necessary in many important chemical industries: 15  Historical overview ◼ Vitalism (Vital force) ◼ In 1811, Swedish scientist, J. Berzelius ◼ Destroy of the Vitalism: ◼ In 1824, a German scientist F. Wohler, pupil of Berzelius was able to prepare oxalic acid from an inorganic substance (CN-CN) dicyanogen ◼ In 1828 Wohler synthesized the substance of animal origin urea (carbamide) from ammonium cyanate (NH4CNO). 16 ◼ Soon other organic substances were synthesized in the laboratory: ◼In 1845 in Germany, H. Kolbe synthesized acetic acid. ◼In 1854 in France, M. Berthelot prepared a fat synthetically. ◼In 1861 in Russia, A. Butlerov synthesized a saccharide substance, and so on. 17  Chemistry of Carbons ◼ At present, with the development of the synthesis of organic compounds and destroy of Vitalism the name organic chemistry remained. The peculiarities of organic compounds depend only on the nature of their principal constituent of carbon. So, organic chemistry is defined as the chemistry of carbon compounds. 18  Main features of organic compounds 1. They consist mainly of carbons. 2. The covalent bond is the major bond between the atoms in their molecules. 3. They are mainly non-electrolytes, don't ionize in solution. 4. They are comparatively slowly react with one another. 5. They have low melting point. 6. They are burn with complete transformation into CO2, water, and nitrogen liberated in Free State, when heated in the presence of the oxygen of the air or other oxidizing agents. 7. They exhibit the phenomena of isomerism. 8. They characterized by the presence of functional groups. 19  STRUCTURE OF ORGANIC COMPOUNDS 20  Structure of atom Bohr- Rutherford model 21 # electrons  Quantum mechanics theory De Broglie’s and Schrödinger ◼ The electron waves are standing wave. ◼ The electron can have many different wave forms, wave pattern, which called orbitals. ◼ The orbitals have a characteristic energy and shapes. ◼ Energy is important because of the atom fined in the most stable state (ground state), which the electron wave forms having the lowest possible energy. ◼ Shapes are important because the amplitude of wave atom particular location is related to the likelihood of finding the electron their (the probability of finding the electron). 25 2 electrons one orbital 8 electrons one + 3 orbital 18 electrons one + 3 + 5 orbitals  QUANTUM NUMBERS There are four quantum numbers characterized the electron wave orbitals: ◼ 1- The principal quantum number ''n'' ◼ ''n'' is positive integral values 1, 2, 3… ∞ ◼ It also identified by letters K, L, M, N, O, P, Q… ◼ The higher the value of ''n'', the farther the electron average distance from the nucleus. ◼ 2- The secondary quantum number ‘’l‘’ ◼ It divides the shell into sub-shell. The value of ''n'' determine the value of ''l'' i.e. l = n-1. It also identified by letters s, p, d, f… 31 ◼ 3- The magnetic quantum number ''m'' ◼ It splits the sublevel into individual orbitals. It describes how can orbitals oriented in the space relative to other orbital its value range from –l to +l. It gives the number of orbital in the sub-shell i.e. s have 1 spherical orbital, p have 3 orbitals, d have 5 orbitals and f have 7 orbitals as shown in figure. 32 ◼ Spin quantum number ''ms'' ± ½ ◼ It gives both the maximum number of electron in a particular orbital and how orbital having the same energy can be fielded. 33 ELECTRONIC CONFIGURATION OF ATOMS ◼ Pauli Exclusion Principle: no two electrons in any given atom can have exactly the same set of 4 quantum numbers; i.e. no atomic orbital may be occupied by more than two-electrons. ◼ Hund’s Rule: the distribution of electrons within the limits of an energy sublevel at which the absolute value of the total spin of the atom is maximum corresponding to the stable state of an atom. i.e. 2- electrons do not occupy a given orbital till all the orbitals of equal energy have at least one-electron. 34 ◼ C12: 1s2 2s2 2p2 6 ◼ N14: 1s2 2s2 2p3 7 ◼ O16: 1s2 2s2 2p4 8 35  CHEMICAL BONDS ◼ It is the forces that hold group of atoms together and make them function as a unit (A MOLECULE). ◼ Type of chemical bonds: 1. Ionic. 2. Covalent. 3. Co-ordinate. 4. Metallic. 5. Van-der Waals forces. 6. Hydrogen bond. 36  1- IONIC BONDS ◼ It occurs when metals react with non-metals. ◼ e.g. Sodium Chloride formation Na Na + e Cl + e Cl Atom Ion Atom Ion loss a valency electron accept this electron electrostatic force Na + Cl NaCl ◼ Electrostatic force = E = 203x10-19 J.nm (Q1Q2/ r) 37 ◼ Bond length is the distance where the energy (repulsion and attraction) is minimum as possible. 38  2- COVALENT BONDS ◼ It is a sharing of two or more electrons with each other to reach into the state of noble gases and the pairs sharing electron are pulled of two nuclei:.. H + H H :H or H H H H H H C H C C H C C H H H H Methane Ethylene A cetylene 39 ◼ Electronegativity: it is the ability of an atom in a molecule to attract shared electron to it. 40  Type of covalent bond ◼ Pure covalent bond '' Non-polar covalent bond'': ◼ It is occurred when the difference of electronegativity between two atoms form the covalent bond equal zero. ◼ Polar covalent bond: ◼ It is occurred when the difference in electronegativity between two atoms form the covalent bond is intermediate. The polarity increases as the difference in electronegativity increases. The difference in electronegativity leads to a dipole molecule. The dipole moment (μ) = amount of charge x distance between charge. − +   Cl H 41  3- Co-ordinate bonding (Dative Covalent) ◼ It is a covalent bond (a shared pair of electrons) in which both electrons come from the same atom. The arrow points from the atom donating the lone pair to the atom accepting it. 42  4- METALIC FORCE ◼ Valence electrons in metals are rampant. ◼ They are not restricted to certain atoms or bonds. ◼ Rather they run freely in the entire solid, providing good conductivity for heat and electric energy. ◼ This behavior of electrons gives special properties such as ductility and mechanical strength to metals. ◼ This is sometimes described as "an array of positive ions in a sea of electrons". Ass. Prof. Dr. Abd-Allah Sh. El- 43 Etrawy  Van der Waals' forces ◼ It is important to remember that van der Waals' forces are forces that exist between molecules of the same substance. They are quite different from the forces that make up the molecule. The van der Waals' forces are the forces that exist between the millions of separate molecules, and not between the hydrogen and oxygen atoms. The van der Waals' forces are very weak. 44  6- Hydrogen bond A hydrogen bond is a dipole interaction that occurs between any molecule with a bond between a hydrogen atom and any of oxygen/fluorine /nitrogen etc. Types of hydrogen bond Intermolecular H-bond Intramolecular H-bond 45  H H H O O O O H H H H H Intermolec ular hy drogen bond H + H + H −  −    R N H N H N H R R R + R + R − +     R N H N− H N H H −   R R C O H O Intramolecular hydrogen bond Salycildahyde 46 HYBRIDIZATION 47 ◼ Hybrid orbital: is a mixing of atomic orbital (s, p and d) to give new ones. ◼ These formed orbitals are stretched out and more able to overlap with neighboring atoms, which leads to the formation of stronger chemical bond. ◼ In quantum mechanism ◼ Orbital hybridization in its simplest term is nothing more than a mathematical approach that involves the combining of individual wave functions for s, p orbitals to obtain wave function for new orbitals. ◼ The new orbitals have in varying proportions the properties of the original orbitals taken separately. ◼ N.B. numbers of the orbital in the hybridization = numbers of the orbitals yielded. 48  Different types of hybridization sp3 sp2 sp 49  3 sp -HYBRIDIZATION 50 51  2 sp -HYBRIDIZATION 52 53 sp-HYBRIDIZATION 54  H―C≡C―H Ethyne (acetylene) Ass. Prof. Dr. Abd-Allah Sh. El- 55 Etrawy  summary Ass. Prof. Dr. Abd-Allah Sh. El- 56 Etrawy  Comparison between () and () bonds ◼Sigma () ◼Pi () 1 Formed by linear overlap Formed by lateral (side to side overlap). (end to end overlap) i.e Less effective overlap. effective overlap 2 Cylindrically symmetrical High electron density below and above about the intermolecular axis the plane of the molecule 3 Has free rotation No free rotation (restricted) 4 Formed of low energy Formed of high energy orbitals, thus of higher energy 5 Only one sigma bond can One or two pi bonds can exist between exist between two atoms two atoms 6 Sigma bonded electrons are Pi electrons are more exposed, more held more tightly between the vulnerable to external effects 57 atomic nuclei (localized) (delocalized) i.e. more polarized Some Consequences of Hybridization 58  Effect on bond strength: ◼ 2S orbital electrons are found closer to the nucleus than 2p electrons. ◼ For this reason a hybrid orbital with a greater proportion of s character is of lower energy and is closer to the nucleus than a hybrid orbital with less s character. Characteristics of Sp3 Sp2 Sp S% character 25 33 1/3 50 C-C bond strength 90 174 231 kcal/mol kcal/mol kcal/mol C-H bond length 1.09 Å 1.08Å 1.06Å 59 Acidic properties In general, the greater the amount of s- character in hybrid orbital containing a pair of electrons, the less basic is that pair of electrons, and the more acidic is the corresponding conjugate acid. Base CH3‫ـ‬ CH4 Acid Strength methanide CH2=CH2 strength CH2=CH:‫ـ‬ HCCH ethylenide HCC:- Acetylendia 60 Illustrate the type of σ-bonds at indicated carbon-carbon bond(s) CH3 Label the hybridization state at indicated carbon atoms. 61  n ks Tha Tha nks Thanks Th k s an n ks h a T 62