Pharmaceutical Organic Chemistry I PC101 Lecture Notes PDF

Pharmaceutical Organic Chemistry I PC101 Introduction for Organic Chemistry Mona S. El-Zoghbi, Ph. D. Pharm. Sc. Associate professor of pharmaceutical Chemistry Pharmaceutical Chemistry Department [email protected] Intended...

Pharmaceutical Organic Chemistry I PC101 Introduction for Organic Chemistry Mona S. El-Zoghbi, Ph. D. Pharm. Sc. Associate professor of pharmaceutical Chemistry Pharmaceutical Chemistry Department [email protected] Intended learning outcomes of the course (ILOs) On successful completion of the course, you should be able to: ❖Recognize several organic terms. ❖Underline the different types of chemical bonds. ❖Recognize the different classes of organic compounds. ❖Assess the structural feature of organic compound and its IUPAC name. ❖Demonstrate alkanes, alkenes, alkynes and alkyl halides (nomenclature, physical and chemical properties, preparation and chemical reactions). ❖ Classify different reaction mechanism. ❖ Outline fundamental principles and applications of stereochemistry, stereo-dynamic, hydroxyl and carbonyl compounds. ❖ Identify the principles of aromaticity and benzenoid compounds. 1. Which of the following rules states that “In the ground state of an atom or ion, electrons fill subshells of the lowest available energy, then they fill subshells of higher energy”? a. Octet rule b. Aufbau Rule c. Pauli Exclusion rule d. Hunds Rule 2. Which of the following is monovalent atom? a. Oxygen b. Nitrogen c. Argon d. Fluorine 3. How many covalent bonds does carbon form? a. 2 b. 3 c. 4 d. None, it dose not form covalent bond lone pair It refers to a pair of valence electrons that are not shared with another atom and is sometimes called a non-bonding pair. Lone pairs are found in the outermost electron shell of atoms. The Shape of Molecules The three-dimensional shape or configuration of a molecule is an important characteristic. Methane Ammonia Water 1. Shape of molecules without lone pair of electron Bonding Bond Configuration Example groups Angles Tetrahedral 4 109.5º Trigonal 3 120º Linear 2 180º Isomers Different compounds having the same molecular formula  Structural Formulas for C 4H10O Isomers (as example) Kekulé Formula Condensed Formula Structural Formula Shorthand or line formula or skeletal formula Resonance is a way of describing delocalized of pi electrons within certain molecules or polyatomic ions where the bonding cannot be expressed by one single structure. NB: The double headed arrow being the unique symbol for resonance. There are different groups of carbon atoms: A primary carbon (1º) is one that is bonded to no more than one other carbon atom. A secondary carbon (2º) is bonded to two other carbon atoms. Tertiary (3º) and quaternary (4º) carbon atoms are bonded respectively to three and four other carbons. Ex. What is the total number of tertiary carbons found in the following compound? Intermolecular Forces All atoms and molecules have a weak attraction for one another, known as van der Waals attraction forces. If there were no van der Waals forces, all matter would exist in a gaseous state. 1.Dipole–dipole attraction force. attractive forces between the positive end of one polar molecule and the negative end of another polar molecule. 2. Hydrogen Bond Electrostatic attraction between a hydrogen (H) which is bound to a more electronegative atom such as nitrogen (N), oxygen (O), or fluorine (F), and another adjacent atom bearing a lone pair of electrons. The hydrogen bond is weaker than an ordinary covalent bond but is much stronger than the dipole–dipole interactions.  Hydrogen bonding accounts for the fact that ethyl alcohol has a much higher boiling point (78.5°C) than dimethyl ether (24.9°C) even though the two compounds have the same molecular weight. ✓ Molecules of ethyl alcohol, because they have a hydrogen atom covalently bonded to an oxygen atom, can form strong hydrogen bonds to each other. ✓ Molecules of dimethyl ether, because they lack a hydrogen atom attached to a strongly electronegative atom, cannot form strong hydrogen bonds to each other. ✓ In dimethyl ether the intermolecular forces are weaker dipole–dipole interactions only. Q1. Which among the following compounds cannot form hydrogen bond? Solubility of organic compounds in Water Many organic compounds, especially alkanes and other hydrocarbons are nearly insoluble in water. Organic compounds that are water soluble, such as ethanol and acetone, generally have hydrogen bond acceptor and donor groups. Hydrophilic moiety polar, hydrogen bonding moieties Hydrophobic moiety nonpolar species Chemical Reaction: A transformation of the reactants into the reaction products Reactant It is the organic compound undergoing change in a chemical reaction. Product It is the final result of the chemical reaction Reaction Conditions The environmental conditions, such as temperature, pressure, catalysts & solvent, under which a reaction progresses optimally. Catalysts These are substances that accelerate the rate of a chemical reaction without themselves being consumed. Classes of Organic Chemical Reactions 1-Classification by Structural Change Addition, Elimination, Substitution and Rearrangement Addition: In an addition reaction the number of σ-bonds in the substrate molecule increases, usually at the expense of one or more π-bonds. Elimination reactions: the number of σ-bonds in the substrate decreases, and new π-bonds are often formed. Substitution: replacement of an atom or group (Y) by another atom or group (Z). In this reaction, the number of bonds does not change. A rearrangement reaction generates an isomer, and again the number of bonds normally does not change. Exercise: 2-Classification by Reaction Type Oxidation and Reduction Reactions If the number of hydrogen atoms bonded to a carbon increases, and/or if the number of bonds to more electronegative atoms decreases, the carbon in question has been reduced. If the number of hydrogen atoms bonded to a carbon decreases, or if the number of bonds to more electronegative atoms increases, the carbon in question has been oxidized. Reduced= blue Oxidized= red  3-Classification by Functional Group Functional Class Formula Characteristic Reactions Substitution (of H, commonly by Cl or Br) Alkanes C–C, C–H Combustion (conversion to CO2 & H2O) Addition Alkenes C=C–C–H Substitution (of H) Addition Alkynes C≡C–H Substitution (of H) Substitution (of X) Alkyl Halides H–C–C–X Elimination (of HX) Substitution (of H); Substitution (of OH) Alcohols H–C–C–O–H Elimination (of HOH); Oxidation (elimination of 2H) Ethers (α)C–O–R Substitution (of OR); Substitution (of α–H) Substitution (of H); Amines C–NRH Addition (to N); Oxidation (of N) Benzene Ring C6H6 Substitution (of H) Addition Aldehydes (α)C–CH=O Substitution (of H or α–H) Addition Ketones (α)C–CR=O Substitution (of α–H) Substitution (of H); Substitution (of OH) Carboxylic Acids (α)C–CO2H Substitution (of α–H); Addition (to C=O) (α)C–CZ=O Substitution (of Z); Substitution (of α–H) Carboxylic Derivatives (Z = OR, Cl, NHR, etc.) Addition (to C=O) Factors that Influence Reactions 1. Type of chemical bond: Compounds constructed of strong covalent bonds are more stable than compounds incorporating one or more relatively weak bonds. 2. Electronic Effects: The distribution of electrons at sites of reaction (functional groups) is a particularly important factor. An inductive effect A resonance effect 3. Steric Effects: Atoms occupy space. When they are crowded together, van der Waals repulsions produce an unfavorable steric hindrance. Ex. The steric effect of tri-(tert- butyl)amine makes electrophilic reactions, like forming the tetraalkylammonium cation, difficult. It is difficult for electrophiles to get close enough to allow attack by the lone pair of the nitrogen (nitrogen is shown in blue) 4. Solvent Effects: Most reactions are conducted in solution, not in a gaseous state. The solvent selected for a given reaction may exert a strong influence on its course.  Mechanisms of Organic Reactions Reaction mechanism A detailed description of the changes in structure and bonding that take place in the course of a reaction Chemical reactions involve the breaking and making of bonds In general, two kinds of curved arrows are used in drawing mechanisms: A full head arrow indicates complete movement or shift of an electron pair: A half headed arrow indicates the shift of a single electron: Homolysis If a covalent single bond is broken so that one electron of the shared pair remains with each fragment Heterolysis If the bond breaks with both electrons of the shared pair remaining with one fragment  In representing reaction mechanism, curved arrows must start from an electron rich species which may be a negative charge, a lone pair, or a bond. Arrowheads must direct towards an electron deficient species which may be positive charge, the positive end of polarized bond The Reaction Arrow The Equilibrium Arrow The Resonance Arrow Reaction Arrow 2 H2 + O2 2 H2O + Energy O O OH + H2O O + H3O Equilibrium Arrow H3C H3C H H Resonance Arrow C O C O H H Reactive Intermediates (Transient The products of bond breaking are not stable and cannot be intermediates) isolated for prolonged study Electrophiles An electron deficient atom or molecule that has an affinity for an electron pair, and will bond to a base or nucleophile. E.g. RCHO Nucleophiles An atom or molecule that has an electron pair that may be donated in bonding to an electrophile. E.g. R-NH2, R-O-H Electron deficient groups are attracted to electron rich groups. Carbocations are electrophiles Carbanions are nucleophiles  Carbenes have only a valence shell sextet of electrons and are therefore electron deficient so, it considered electrophiles. Carbon radicals (free radicals) have only seven valence electrons, and may be considered electron deficient; however, they do not in general bond to nucleophilic electron pairs, so their chemistry exhibits unique differences from that of conventional electrophiles. Examples for electrophiles and nucleophile Ex. Which of the following is an electrophile? A. CH3CH3 B. CH3CH2+ C. CH3CH2. D. H2O  Hybridization in organic compounds Hybridization is the term applied to the mixing electrons of atomic unequivalent orbitals in an atom to generate a set of new equivalent hybrid orbitals. 1.SP3 hybridization (CH4)  Mixing of the electron in 2S with the three electrons of 2P produced 4 SP3 hybrid orbitals available to make 4 sigma bonds form four sigma bonds with 4 hydrogen atoms through head to head overlapping have the tetrahedral shape. 2. SP2 hybridization (C2H4)  Ethylene molecule contains a C=C and has planner geometry Only 2Px and 2Py orbitals combine with the 2S orbital while the 2Pz orbital remains unchanged and appears perpendicular to the plane of the 3 hybrid orbitals Each carbon atom use the 3 SP2 hybrid orbitals to form 2 bonds with 2 Hydrogen atoms and the last orbital of SP2 type to form bond with the adjacent carbon by head to head overlapping The 2 unhybridized Pz orbitals form double bond (π bond) by sideway overlapping 3. SP hybridization (C2H2)  Acetylene molecule has a linear geometry, contains a carbon carbon triple bond hybridization take place between the remaining electron in 2S orbital and the electron in 2Px to produce 2 hybrid orbital of SP type. 2Py and 2Pz orbitals remains unhybidized. The 2 Sp hybrid orbitals of each carbon form sigma bond with one hydrogen atom and sigma bond with the adjacent carbon by head to head overlapping. An additional two bi bonds formed by the sideway overlapping between the two 2Py and 2PZ unhybridized orbitals of each carbon. Which of the following line structures match the below condensed structural formula? (CH3)3CCH2CH(CH3)C2H5 1. Differntiate between ionic and covalent bond 2. Draw the electronic configuration of fluorine atom (its atomic No.=9) 3. What type of chemical bonding will be found in magnesium oxide? 4. Which of the following is an electrophile? a) CH4 CH + c) OH- d) H b) 3 2O 5. ………………. is a trivalent atom (valence of this atom is 3). a) Carbon b) Nitrogen c) Oxygen d)Fluorine 6. Mark the hydrogen bond donor?  Which of the following reactions is an addition reaction? Which of the following line structures match the below condensed structural formula? (CH3)3CCH2CH(CH3)C2H5  What is the total number of tertiary carbons found in the following compound? Which among the following compounds cannot form hydrogen bond? A compound having a bond angle 180° is…………………… A. Alkyne B. Alkene C. Alkane D. Cycloalkane  Which of the following structures is incorrect? How many covalent bonds does carbon form? A. 2 B. 3 C. 4 D. None, it dose not form covalent bond The following reaction is ………………..  Determine the aldehydic species Alkanes react mainly through? a) Addition b) Elimination c) Substitution d) Rearrangement Which structural formula is not an isomer of the molecular formula C5H10O?