Organic Chemistry PSMA 411 PDF

8/23/2021 OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Checklist:...

8/23/2021 OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Checklist: Read course and unit objectives. Read study guide prior to class attendance. Organic Chemistry Read required learning resources, refer to unit terminologies for jargons. PSMA 411 Proactively participate in discussions. Answer and submit unit course tasks. Learning Outcomes: Topic Outline: At the end of this unit, the students are expected I. Introduction to Organic Chemistry to: II. Physicochemical Properties Define organic chemistry and its scope. Differentiate inorganic compounds from organic III. Isomerism compounds. IV. Hydrocarbons Differentiate the types of isomers and stereoisomers. I. Hydrocarbon Derivatives Draw the general structures of the different functional groups. Branch of chemistry that deals with Organic carbon-containing compounds Chemistry ✔ except carbonates, bicarbonates, Urea (CH₄N₂O) cyanides and oxides AKA Carbamide Organic Compounds Inorganic Compounds “Wöhler synthesis” – heated inorganic compound Flammable Non-flammable ammonium cyanate produced urea Low melting point High melting point Low boiling point High boiling point Soluble in non-polar Insoluble in non-polar solvents solvents Insoluble in water Soluble in water Covalent Bonding Ionic Bonding Many atoms Few atoms 1  8/23/2021 History Uniqueness of Carbon In 1828, Friedrich Wohler, a German chemist, disproved the Carbon is able to form Ability to Catenate “Vitalism” theory which states 4 covalent bonds (4 Carbon atoms link that all organic compounds come valence electrons) with together to form from living things. He was able to other carbon or other chains of varying isolate urea from an inorganic elements. length, branched compound, ammonium cyanate. Carbon atoms have the chains and rings of ability to bond to each different sizes other to form long chains or rings. Atomic Structure Elements: Fundamental building blocks of all substances Atoms: Smallest particle of an element Neutron: Neutral subatomic particle Proton: Positively charged subatomic particle (+1 charge) Electron: Negatively charged subatomic particle (-1 charge) Nucleus: Center of an atom; contains protons and neutrons An atom consists of a nucleus surrounded by electrons that are equal in number to the protons of the nucleus Atomic Number and Atomic Mass Isotopes The atomic number (Z) atoms of the same element with different number of protons in numbers of neutrons and thus different mass nucleus number (A). The mass number (A) number of protons plus neutrons 2  8/23/2021 ORBITALS Atomic Structure region of space where there is a Determine the number Orbitals certain probability of finding an electron of protons, neutrons Can hold 2 electrons and electrons present Also known as WAVE FUNCTION in atoms of the following: Atomic Structure Distribution of Orbitals within Orbitals Shells Each shell contains subshells known as atomic orbitals. Electrons are said to occupy orbitals in an atom. No. of orbitals of Maximum number of Subshell equal energy electrons s 1 p 3 d 5 f 7 Distribution of Orbitals within Orbital Shells Relative Orbitals Maximum number energies of Shell contained In of electrons shell electrons in each shell can hold each shell one 4s three 4p 4 2 + 6 + 10 + 14 = 32 five 4d seven 4f orbitals one 3s 3 three 3p 2 + 6 + 10 = 18 five 3d orbitals one 2s 2 2+6 =8 three 2p orbitals 1 one 1s 2 3  8/23/2021 Electron Principles AUFBAU PRINCIPLE states that electrons fill lower-energy atomic orbitals before filling higher-energy ones PAULI’S EXCLUSION PRINCIPLE maximum of 2 electrons can occupy the same orbital only if they have opposite spins HUND’S RULE for degenerate orbitals, electrons fill the orbitals singly before they pair up HEISENBERG’S UNCCERTAINTY PRINCIPLE No 2 electrons can have the same set of 4 quantum numbers Quantum Numbers Electron Configuration SYMBOL VALUES FUNCTION symbolic notation of the manner in which the Determine the size electrons of its atoms are distributed over different 1. PRINCIPAL QN n 1,2,3 of the particle atomic orbitals Subshell or summary of where the electrons are around a 2. AZIMUTHAL or sublevel, nucleus l 0 to (n-1) ANGULAR determines the shape orbitals, 3. MAGNETIC m or ml -1 to +1 determines orientation -1/2 to direction of spin or 4. SPIN s or ms +1/2 orientation Electron POP QUIZ: Write ground-state Configuration electron configurations for these elements. RULES a. Lithium 1. Lowest-energy orbitals fill first: 1s 🡪 2s 🡪 2p 🡪 3s 🡪 3p 🡪 4s 🡪 3d (Aufbau “build-up” principle) 2. Electrons act as if they were spinning around an axis. b. Oxygen Electron spin can have only two orientations, up ↑ and down ↓. Only two electrons can occupy an orbital, and they must be of opposite spin (Pauli exclusion principle) to have unique wave equations. 3. If two or more empty orbitals of equal energy are c. Chlorine available, electrons occupy each with spins parallel until all orbitals have one electron (Hund’s rule) 4  8/23/2021 Chemical Bonding Chemical Bonding Octet rule – atoms react in a way that achieve joining of two atoms in Atoms form bonds valence shell of eight valence electrons. a stable arrangement because the resulting compound is more IONIC BOND may occur between stable than the bond between anion and cation atoms of the same or separate atoms atom may lose or gain enough electrons to acquire a different elements. Ionic bonds in salts completely filled valence shell favorable process form by electron anions (-) gain electrons; cations (+) lose electrons because it always leads transfers to lowered energy and Organic compounds increased stability have covalent bonds from sharing electrons Covalent Bonding FORMATION OF IONS LEWIS STRUCTURE Octet Rule – The tendency among atoms of group 1A-7A Electron dot structure elements to react in ways that achieve an outer shell of Valence shell electrons of an atom are represented eight valence electrons. as dot Anion – an atom or group of atoms bearing a negative charge. Cation – an atom or group of atoms bearing a positive KEKULE STRUCTURE charge. Line bond structure Each shared electron is represented by line between the atom symbols LEWIS STRUCTURE H has one bond C has four bonds N has three bonds and one unshared pair of electrons O has two bonds and two unshared pair of electrons F, Cl, Br, and I have one bond and three unshared pairs of electrons. 5  8/23/2021 POP QUIZ Covalent Bonding Draw Lewis structures, showing all valence Lone-pair electrons or non-bonding electrons electrons, for these molecules: Pair of valence electrons that are not used for bonding a. H2O2 b. CH3OH c. CH3Cl Multiple Bond Identifying Formal Charges When 2 atoms share more than 1 pair of electron Formal Charge DOUBLE BOND Associated with any atom that does not exhibit the TRIPLE BOND appropriate number of valence electrons. 1st: Determine the number of valence electrons *C2H4 2nd: Determine whether the atom exhibits appropriate number of electrons *C2H2 FC = [# valence e-] – [non-bonded e- + number of bonds] Determine the formal charge of Electronegativity and Bond Polarity the following molecule ELECTRONEGATIVITY Measure of the ability of an atom to attract electrons 6  8/23/2021 Induction and Polar Covalent POP QUIZ Bonds Based on the relative positions in the periodic Difference in electronegativity < 0.5 table, which element in each pair has the larger Non-polar covalent bond electronegativity? Equally shared electrons between the 2 atoms a. Lithium or Carbon b. Carbon or Oxygen c. Nitrogen or Oxygen POP QUIZ: Identify polar covalent Induction and Polar Covalent bonds and show any partial charges Bonds that result from inductive effects Difference in electronegativity 0.5-1.7 polar covalent bond not equally shared electrons between atoms INDUCTION withdrawal of electrons towards a highly electronegative atom which causes the formation of partial charges LEWIS STRUCTURE Difference in electronegativity >1.7 H has one bond ionic bond C has four bonds electrons are not shared N has three bonds and one unshared pair of electrons NaOH O has two bonds and two unshared pair of electrons F, Cl, Br, and I have one bond and three unshared pairs of electrons. 7  8/23/2021 Drawing Chemical Structures Shorthand ways of writing structures Expanded Condensed Skeletal Expanded Condensed Skeletal Expanded Condensed Skeletal 8  8/23/2021 Physical Property Intermolecular Forces A property that does not affect the chemical The physical properties of molecules are in part dependent on the type's of intermolecular forces (IMF) present. identity of a compound Boiling points (BP) are also dependent on the mass of the Can be observed and measured without changing a molecule. compound’s composition of matter Solubility, the ability to dissolve into a solvent is dependent Any substance that has mass and can occupy space on IMFs. The strength of the interaction between molecules is also dependent on the overall shape of the molecule. There are 3 types of IMFs, by decreasing strength they are: 1) Hydrogen bonding 2) Dipole-dipole 3) Van der Waals or London Dispersion Hydrogen Bonding Hydrogen Bonding Hydrogen bonding is a complex interaction that Occur primarily between OH, NH and FH. The more EN the includes dipole-dipole, as well as orbital interactions atom the stronger the interaction. (The atom H is attached to usually has a lone pair of e-) and the transfer of electron density between molecules. Geometry: X-H ----:X- These are the strongest of the IMFs and range from 5 – 25 kJ/mol Dipole-Dipole Dipole-Dipole Dipole-dipole forces arise from the attraction of oppositely charged atoms (other than H) in molecules. These molecules may have a permanent dipole moment. Generally in organic molecules they results from the presence of C-X bonds where X is more electronegative that C. These are generally weaker than H-bonding, ranging from about 5-10 kJ/mol. 9  8/23/2021 Van der Waals Structural Effects on IMFs Van der Waals or (London) dispersion forces arise The strength of the IMFs from the movement of electrons within a molecule. depend on the amount of This natural motion can produce an uneven contact between the distribution of the electrons (polarization of the molecules, especially for distribution) resulting in a temporary dipole dispersion forces. Hence moment in the molecule. This will induce the the shape of the movement of electrons in adjacent molecules molecule can affect the producing a dipole moment in them. surface area of contact, These “induced” dipole moments are very brief as they long thin molecules have disappear when the electrons move to new locations within the molecule, so they forces are very brief and more surface in contact weak, only 2-5 kJ/mol. than spherical molecules. Factors Affecting the Physical Properties of Organic Compounds Structure of Functional Group Molecules having a polar functional group have a higher b.p. than others with a non-polar functional group of similar molecular masses. Length of Carbon Chains Molecules with higher molecular masses have higher m.p., b.p. and density Higher molecular masses 🡪 Large molecular sizes 🡪 Stronger London dispersion forces among molecules 10  8/23/2021 Length of Carbon Chains Length of Carbon Chains Molecules with branched chains As a rule, larger molecules have higher boiling (and 🡪 b.p. and density lower than its straight-chain melting) points. isomer Straight-chain isomers have greater surface area in contact with each other 🡪 Greater attractive force among the molecules Solubility Solubility If the solvent is polar, like water, then a smaller Any functional group that can donate a hydrogen hydrocarbon component and/or more charged, bond to water (eg. alcohols, amines) will hydrogen bonding, and other polar groups will tend to increase the solubility. significantly contribute to water solubility. The number of Carbons. More carbons means more of Any functional group that can only accept a a non-polar/hydrophobic character, and thus lower hydrogen bond from water (eg. ketones, solubility in water. aldehydes, ethers) will have a somewhat smaller Anything with a charged group (eg. ammonium, but still significant effect on water solubility. carboxylate, phosphate) is almost certainly water soluble, unless it has large nonpolar group, in which Other groups that contribute to polarity (eg. alkyl case it will most likely be soluble in the form of halides, thiols sulfides) will make a small micelles, like a soap or detergent. contribution to water solubility. Boiling Point and Melting Point Chemical Properties Melting and boiling are processes in which A chemical reaction occurs when one substance is noncovalent interactions between identical converted into another substance(s). molecules in a pure sample are disrupted. The A chemical reaction is accompanied by breaking of stronger the noncovalent interactions, the more some bonds and by making of some others. energy that is required, in the form of heat, to break them apart. 11  8/23/2021 Reaction Mechanism Homolytic Fission Define as the detailed knowledge of the steps involved The fission of a covalent bond with equal sharing of in a process in which the reactant molecules change bonding electrons. into products. Chemical reactions involve breaking of one or more of the existing chemical bonds in reactant molecule(s) and formation of new bonds leading to products. The breaking of a covalent bond is known as bond fission. During bond breaking or bond fission, the two shared Free radicals are neutral but reactive species having an electrons can be distributed equally or unequally unpaired electron and these can also initiate a chemical between the two bonded atoms. reaction. Heterolytic Fission Heterolytic Fission The fission of a covalent bond involving unequal sharing of The charged species obtained by the heterolytic fission bonding electrons. initiate chemical reactions and they are classified as This type of bond fission results in the formation of ions. electrophiles and nucleophiles. The ion which has a positive charge on the carbon atom, is Electrophiles: An electrophile is an electron deficient known as the carbonium ion or a carbocation. On the other species and it may be positively charged or neutral. hand, an ion with a negative charge on the carbon atom is Examples are H+ , AlCl3 , Br2 , Cl2 , Ag+ , CH3 +, BF3 known as the carbanion. etc. Nucleophiles : A nucleophile is negatively charged or electron rich neutral species. Examples of nucleophiles are OH– , –NO2+ , H2O, :NH3 etc. Types of Reactions in Organic Compounds Substitution A substitution reaction involves the displacement of one atom or group in a molecule by another atom or group. Aliphatic compounds undergo nucleophilic substitution reactions. For example, a haloalkane can be converted to a wide variety of compounds by replacing halogen atom (X) with different nucleophiles as shown below. 12  8/23/2021 Types of Reactions in Types of Reactions in Organic Compounds Organic Compounds Another type of substitution reaction which takes place Elimination in an aromatic hydrocarbons. In this case, an An elimination reaction is characterized by the removal electrophilic reagent attacks the aromatic ring because of a small molecule from adjacent carbon atoms and the the latter is electron rich. The leaving group, in this case, formation of a double bond. is always one of the hydrogen atom of the ring. Types of Reactions in Types of Reactions in Organic Compounds Organic Compounds Addition Molecular Rearrangements Unsaturated hydrocarbons such as alkenes and alkynes proceeds with a fundamental change in the are extremely reactive towards a wide variety of hydrocarbon skeleton of the molecule. During this reagents. The carbon-carbon double bond (–C=C–) of an reaction, an atom or group migrates from one position alkene contains two types of bonds. In alkynes, three to another. carbon-carbon bonds. These are compounds with the same molecular formula and same molecular Structural Isomers: Isomers weight but different structural formula, this differ in physical and chemical properties Chain Isomers Same molecular formula, but different arrangements STRUCTURAL of the carbon ‘skeleton’. ISOMERS The positions of the carbon atoms can be rearranged to ISOMERS ENANTIOMERS give ‘branched’ carbon chains coming off the main STEREOISOMERS chain. The name of the molecule DIASTEREOMERS changes to reflect this, but the molecular formula is still the same. https://www.compoundchem.com/2014/05/22/typesofisomerism/ 13  8/23/2021 Structural Isomers: Structural Isomers: Positional Isomers Functional Isomers Same molecule formula; Same molecular formula same functional group, but but the atoms are its position in the molecule rearranged to give a changes. different functional group. The name of the molecule The name of the molecule changes to reflect the new changes to reflect the new position of the functional functional group. group. https://www.compoundchem.com/2014/05/22/typesofisomerism/ https://www.compoundchem.com/2014/05/22/typesofisomerism/ Constitutional isomers Stereoisomerism Positioning the different functional groups in their Same atoms but linked together differently sites of action Three main groups: 1. Optical Isomer ENANTIOMER – D and L forms DIASTEREOMER ex. Epimers 2. Geometric Isomers Cis and Trans 3. Conformational Isomers Same MF Boat and Chair different connectivity Optical isomers H contain at least one asymmetric, or chiral, carbon atom H Chiral - carbons that have four non-identical substituents around it (chiral center or stereogenic center) H Each asymmetric carbon atom can exist in one of two non-superimposable isomeric forms 14  8/23/2021 (S)-citalopram + (R)-citalopram = CITALOPRAM POP QUIZ: Chiral or non chiral ESCITALOPRAM POP QUIZ: Chiral or non chiral POP QUIZ: Chiral or non chiral 15  8/23/2021 Stereoisomers: POP QUIZ: Chiral or non chiral Enantiomers and Diastereomers Enantiomers are mirror images of each other and non- sumperimposable, Diastereomers are not mirror images of each other and non-superimposable Stereoisomers: Stereoisomers: Enantiomers and Diastereomers Epimers Enantiomers are mirror images of each other and non- Isomers differing as a result of variations in configuration sumperimposable, of the —OH and —H on carbon atoms 2, 3, and 4 of glucose Diastereomers are not mirror images of each other are known as epimers and non-superimposable Stereoisomers: Stereoisomers: Geometric Isomers Optical Isomers Commonly exhibited by Differ by the placement of alkenes, the presence of different substituents two different substituents around one or more atoms on both carbon atoms at in a molecule. either end of the double Different arrangements of bond these substituents can be Two different non- impossible to superimpose. superimposable isomers due to the restricted rotation of the bond. https://www.compoundchem.com/2014/05/22/typesofisomerism/ https://www.compoundchem.com/2014/05/22/typesofisomerism/ 16  8/23/2021 Stereoisomers: Stereoisomers: Optical Isomers Optical Isomers Differ by the placement of different substituents around one or more atoms in a molecule. Different arrangements of these substituents can be impossible to superimpose. https://www.compoundchem.com/2014/05/22/typesofisomerism/ groups that are spatially and Importance of Isomerism Bioisosteres electronically equivalent and, thus, interchangeable without significantly altering the molecules’ physicochemical properties. Purpose Examples ✔ Enhance desired biological ✔ Fluorine vs Hydrogen or physical properties ✔ Hydroxyl vs Amino Acids ✔ Increased potency ✔ Hydroxyl vs Thiol Groups ✔ Decreased side-effects ✔ Methyl, Methoxyl, ✔ Increase duration of action Hydroxyl, Amino groups vs Hydrogen ✔ Fluoro, Chloro, & Bromo, thiol, vs Methyl & other small alkyl groups https://www.compoundchem.com/2014/05/22/typesofisomerism/ A. Chain Isomers Hydrocarbons Chemical compounds composed Pop Quiz B. Positional Isomers only of hydrogen and carbon atoms C. Functional Isomers 1. 2. 3. 17  8/23/2021 Aliphatic hydrocarbon compounds joined together in straight chains, Aromatic carbocylic compounds containing conjugated double bonds Hydrocarbons branched chains or non-aromatic Hydrocarbons rings Benzene – simplest aromatic hydrocarbon Alkanes Alkenes Alkynes Cyclic August Kekule (1865) Kathleen Lonsdale (1929) paraffins olefins acetylenes Benzene ring as a flat Used X-ray crystallography sp3 hybrid sp2 hybrid sp hybrid prefix – cyclo molecule, having to show carbon-carbon suffix – ane suffix – ene suffix – yne alternating single and bonds in a benzene ring double bonds between are the same length carbon atoms https://www.compoundchem.com/2020/09/07/kekule/ Replacing one of the hydrogens Replacing one of the hydrogens Benzene with a different functional group Benzene with a different functional group Derivatives Derivatives https://www.compoundchem.com/2014/09/01/benzene-derivatives-in-organic-chemistry/ https://www.compoundchem.com/2014/09/01/benzene-derivatives-in-organic-chemistry/ Replacing one of the hydrogens One or more hydrogen atoms in Benzene with a different functional group Hydrocarbon the molecules is replaced by Derivatives Derivatives certain group of atoms Hydroxy Derivatives – alcohols, phenols Ethers Carbonyl Compounds – aldehydes, ketones Carboxylic Acids – monocarboxylic acids, dicarboxylic acids Amides Esters Nitrogen Containing Compounds – amines, nitriles/cyanides Alkyl Halides https://www.compoundchem.com/2014/09/01/benzene-derivatives-in-organic-chemistry/ 18  8/23/2021 With hydroxyl (-OH) functional group Alcohols Prefix – hydroxy Alcohols With hydroxyl (-OH) functional group R-OH Suffix – ol Prefix – hydroxy Suffix – ol According to number of alkyl According to the number of groups attached to the hydroxyl groups Examples Other name Structures hydroxyl-bearing carbon Methanol Wood alcohol Primary Monohydric Ethanol Grain alcohol Secondary Dihydric Phenol Carbolic acid Tertiary Trihydric With hydroxyl (-OH) functional group Alkoxy-substituted alkanes Phenols attached to a carbon atom that is a part Ethers R-O-R of an aromatic ring, Ar-OH Formed by the bimolecular dehydration of alcohols with sulfuric acid Contains at least 1 hydrogen atom Contains two carbon groups bonded to the Aldehydes attached to the carbonyl carbon Ketones carbonyl carbon RC=OH RC=OR Formed by oxidation of primary alcohols Formed by oxidation of secondary alcohols Prefix – oxo Prefix – oxo Suffix – al Suffix – one Examples Other name Structures Examples Other name Structures Methanal Formaldehyde Propanone Acetone Ethanal Acetaldehyde 2-butanone Ethyl methyl ketone Propanal Propionaldehyde 3-pentanone Diethylketone 19  8/23/2021 Carboxylic Produced by oxidation of aldehydes Contains the carboxyl functional group Carboxylic Produced by oxidation of aldehydes Contains the carboxyl functional group Acids RC=OOH Acids RC=OOH Suffix – oic acid Suffix – oic acid Formed by the reactions of acids and Formed by the reactions of organic acids Amides with ammonia or with amides Esters alcohols with acid catalysts Alkyl alkanoate, RC=OOR RC=ONH2 Suffix – oate Suffix – amide Classification Structures Primary Amide Examples Other name Structures Methyl Formate methanoate Secondary Amide Methyl ethanoate Acetate Tertiary Amide Ethyl methanoate Ethyl formate Amines Organic compound derived from ammonia RNH2 Nitriles Organic compound derived from ammonia Cyanides, RCN Prefix – amino Prefix – cyano Suffix – amine Suffix – nitrile Classification Structures Example Structures Primary Amine Ethanenitrile / Acetonitrile Secondary Amine Propanenitrile Tertiary Amine 20  8/23/2021 Derivatives of alkanes in which one Alkyl hydrogen in an alkane is replaced by a Halides halogen RX, X = Cl, Br, I, F Classification Structures Primary Secondary Tertiary Pop Quiz Identify the functional moieties in the figures. Pop Quiz Identify the functional moieties in the figures. Video Links: References: What is Organic Chemistry? By CrashCourse Hart, D. J. (2012). Organic chemistry: A short https://youtu.be/PmvLB5dIEp8 course. Brooks/Cole Cengage Learning. Stereochemistry by CrashCourse https://www.compoundchem.com/ https://youtu.be/Bw_cetheReo https://chem.libretexts.org/ An Overview of Aldehydes and Ketones by CrashCourse https://youtu.be/-fBPX-4kFlw Carboxylic Acid Derivatives by CrashCourse https://youtu.be/VfX2od-AwRo 21  8/23/2021 OUR LADY OF FATIMA UNIVERSITY COLLEGE OF PHARMACY Thank you! Any questions? 22