Fundamental Organic Chemistry I Phan Minh Giang CHE2110E 5pylhvg Chapter 1 INTRODUCTION TO ORGANIC CHEMISTRY Organic Chemistry Organic Chemistry • Organic Chemistry course gives the fundamentals of Organic Chemistry through explanations and examples, emphasizing the relevance of organic chemistry to biological sciences (e.g., medicine, agriculture, nutrition, etc.) and earth sciences. • The primary organization of the course is by functional groups, beginning with the simple (alkanes) and progressing to the more complex. There is also an emphasis on the explaining the fundamental mechanisms of reactions. • The main topics covered in this course: - Classification of organic compounds - Nomenclature of basic classes of organic compounds - Structures and Properties of organic compounds - Chemical transformations of organic compounds - Application of organic compounds Organic Chemistry Introduction to Organic Chemistry • • • • • • • • • • Organic compounds and Organic Chemistry Organic Chemistry and our life Structural diversity of organic compounds Hybridization and the shapes of organic molecules Structural characteristics of organic compounds Stereochemistry Functional Group Interconversions (FGI) C-C bond formation Fundamental mechanisms Synthetic design and strategy Organic Chemistry Important Terms and Concepts Carbon chemistry Carbon compound Structural diversity Structural characteristics Heteroatom Valence Bond (VB) Theory Hybridization Molecular Orbital (MO) Theory Acyclic and Cyclic compound Aliphatic and Aromatic compound Geometry and Shapes of organic compound Stereochemistry Organic Chemistry Organic Compounds and Organic Chemistry More than 27 Organic Chemistry Organic Chemistry • Organic Chemistry is the study of carbon compounds. - Carbon atoms can share four valence electrons and form four strong covalent bonds. - Carbon atoms can bond to one another, forming long chains and rings. - Millions of different organic compounds have been prepared just by combining carbon with hydrogen, oxygen, and nitrogen. - Sulfur, phosphorus, and halogens also appear in organic molecules. • Organic compounds are natural or synthetic. - Bioorganic Chemistry: Organic compounds derived from living organisms. - Organic synthesis: Organic compounds synthesized in the laboratories. Organic Chemistry Structures of Organic Compounds Organic Chemistry Stability of Organic Compounds Organic Chemistry Structures of Organic Compounds Organic Chemistry The Structural Theory of Organic Chemistry Valence (Valency) The power of an atom to combine with others, measured by the number of hydrogen atoms it can displace or combine with. Organic Chemistry Hybridization and Shapes of Organic Compounds Organic Chemistry Introduction to Organic Chemistry Development of Organic Chemistry The structural Theory of Organic Chemistry Study of Organic Chemistry Classification of organic compounds: Functional Groups Representation of organic compounds Organic Chemistry Important Terms and Concepts Single bond and Multiple bond C-C bond in organic compound (chain, cycle, unsaturated and saturated hydrocarbon, derivative) Functional Group Structure and Reactivity Organic Chemistry Development of Organic Chemistry Organic Chemistry Study of Organic Chemistry We study: Organic Chemistry Classification of Organic Compounds Organic Chemistry Classification of Organic Compounds (C, X or C, X) hydrocarbon (C, H) chain Organic Chemistry Functional Groups Organic Chemistry Functional Groups Organic Chemistry Functional Groups Organic Chemistry Hydrocarbons reactive center: carbon-carbon multiple bonds Organic Chemistry Oxygen-containing FGs reactive center: carbon singly bonded to an electronegative atom Organic Chemistry Oxygen-containing FGs reactive center: carbon bonded to an electronegative atom Organic Chemistry Oxygen-containing FGs reactive center: carbon bonded to an electronegative atom Organic Chemistry Sulfur-containing FGs reactive center: carbon singly bonded to an electronegative atom Organic Chemistry Nitrogen-containing FGs reactive center: carbon singly bonded to an electronegative atom Organic Chemistry Nitrogen-containing FGs reactive center: carbon bonded to an electronegative atom Organic Chemistry Halogen-containing FGs reactive center: carbon singly bonded to an electronegative atom Organic Chemistry Functional Groups Practice Organic Chemistry Representation of Organic Compounds Organic Chemistry Representation of Organic Compounds condensed dash bond-line Organic Chemistry Representation of Organic Compounds Bond-line formula: excellent formula for complex molecules Organic Chemistry Representation of Organic Compounds Organic Chemistry Representation of Organic Compounds stereoisomers Organic Chemistry Introduction to Organic Chemistry Chemical bond: the Octet rule Ionic bonds Covalent bonds Electronegativity and Polarization of covalent bonds Dipoles and intermolecular forces Hydrogen bonds (intermolecular and intramolecular) Hybridization Organic Chemistry Important Terms and Concepts Octet rule Electronegativity Covalent bond Polar covalent bond Nonpolar covalent bond Dipole Polar molecule and Nonpolar molecule Dipole-dipole interaction Hydrogen bonding H-bond donor H-bond acceptor Hybridization of atomic orbitals Organic Chemistry Forming Chemical Bonds Valence Bond Theory • A covalent bond forms when two atoms approach each other closely and a single occupied orbital on one atom overlaps a singly occupied orbital on the other. • The electron are now paired in the overlapping orbitals and are attracted to the nuclei of both atoms, thereby bonding the atoms together. How does electron sharing between atoms occur? Organic Chemistry I Chemical Bonds: the Octet Rule How molecules are formed from atoms: Stability Gain! Organic Chemistry Chemical Bonds: the Octet Rule Organic Chemistry Chemical Bonds: Covalent Bonds Organic Chemistry Polarization of Covalent Bond: Electronegativity Electronegativity: the ability of an element to attract electrons. Bond polarization: unequal sharing of electrons in a covalent bond. Polar covalent bond: the driving force of organic chemical reactions. Organic Chemistry Polar Covalent Bond: Dipole Moment Nonpolar covalent bond: difference in electronegativity 0 – 0.4 Polar covalent bond: difference in electronegativity 0.4 – 2.0 Ionic bond: difference in electronegativity > 2.0 nonpolar polar Organic Chemistry Polar Covalent Bond: Dipole Moment Polar molecule has a partially positive end and a partially negative end, it is a dipole, and it has a dipole moment. Organic Chemistry Polar Covalent Bonds and Polar Molecules Organic Chemistry Valence Shell Electron Pair Repulsion (VSEPR) Molecular Geometry (VSEPR) Model Because electron pairs repel each other, the electron pairs of the valence shell tend to stay as far apart as possible. The repulsion between nonbonding pairs is generally greater than between bonding pairs. Bonding pair Organic Chemistry Valence Shell Electron Pair Repulsion (VSEPR) Molecular shapes water primary amine methanol secondary amine dimethyl ether tertiary amine Organic Chemistry Polar/Nonpolar and Geometry of Molecules Organic Chemistry Intermolecular Forces in Biochemistry • Intermolecular forces (cation-anion, covalent bonds, ion-dipole, dipoledipole, Van der Waals) are extremely important in the functioning of cells. They determine the properties of molecules that make up living organisms. • Hydrogen bond formation, the hydration of polar groups, and the tendency of nonpolar groups to avoid a polar environment all cause complex protein molecules to fold in precise ways – ways that allow them to function as biological catalysts of incredible efficiency. Organic Chemistry Dipole-Dipole Interaction: Hydrogen Bonding H2O H2O Molecule-Molecule interaction: b.p. Molecule-Solvent interaction: solvation Organic Chemistry Hydrogen Bonding Model Y: .... H H-bond acceptor X H Z: ..... H Z H-bond donor • Hydrogen bons are very special type of dipole-dipole interaction. • The hydrogen bonds are always indicated by a dotted line. • The strength of a hydrogen bond (3-9 kcal/mol) is about 1/10 strength of a covalent bond (36-125 kcal/mol). Organic Chemistry Hydrogen Bonds Organic Chemistry Hydrogen Bonding in Alcohols and Phenols Organic Chemistry Hydrogen Bonding in Amines NH3 R-NH2 RR’NH RR’R”N Organic Chemistry Hydrogen Bonding in Carboxylic Acids Carboxylic acids have exceptionally high boiling points, due in large part to dimeric associations involving two hydrogen bonds. A structural formula for the dimer of acetic acid is shown here. Organic Chemistry Hydrogen Bonding: Watson-Crick DNA Double Helix 1953: Watson and Crick proposed a double helix as a model for secondary structure of DNA. Organic Chemistry Three-dimensional (3D) Organic Chemistry Jacobus van’t Hoff and Joseph Le Bel (1874): the four bonds of carbon are not randomly oriented but have a specific spatial orientation. Organic Chemistry Why Hybridization of AOs? Organic Chemistry I Hybridization and Geometry of Organic Compounds sp sp2 sp3 Organic Chemistry Valence Bond (VB) Theory and Hybridization Organic Chemistry Valence Bond (VB) Theory and Hybridization Forming covalent bond Organic Chemistry Valence Bond (VB) Theory and Hybridization Forming covalent bond Organic Chemistry Hybridization and Geometry of Organic Compounds Organic Chemistry Hybridization and Geometry of Organic Compounds Linus Pauling, 1931: An s orbital and three p orbitals can combine, or hybridize, to form four equivalent atomic orbitals. Organic Chemistry Hybridization and Geometry of Organic Compounds The structure of ethane The carbon-carbon bond is formed by overlap of two carbon sp3 hybrid orbitals. Organic Chemistry Hybridization and Geometry of Organic Compounds Organic Chemistry Hybridization and Geometry of Organic Compounds In alkyne, the two sp hybrid orbitals of one carbon form sigma bond with a hydrogen and the other sp-hybridized carbon atom. The overlap of the remaining p orbitals gives the double part and triple part of the C-C triple bond. Organic Chemistry Hybridization and Geometry of Organic Compounds Organic Chemistry Hybridization and Geometry of Organic Molecules Organic Chemistry I Hybridization and Geometry of Organic Compounds Assigning hybridization to atoms in a molecule Organic Chemistry Electron Movement and Structural Effects Main electron environments Inductive effect of sigma bond electrons Resonance effect of pi bond electrons Resonance models for delocalization of p electrons Hyperconjugation effect Steric effects (repulsion of electrons through space) Organic Chemistry Electron Movement \and Structural Effects • Main electron environments: electrons can move in a molecule in sigma (single bond), pi (double bond) or lone pair (non-bonding) electronic environment. • Structural effect: The electron movement affects the properties of organic compounds. • Bronsted-Lowry acids and bases: a Bronsted-Lowry acid is a subsance that donates a hydrogen ion (H+). A Bronsted-Lowry base accepts a hydrogen proton. • Lewis acids and bases: a Lewis acid has a vacant valence orbital and can accept an electron pair. A Lewis base is a substance that donates an electron pair. Organic Chemistry Important Terms and Concepts Electron movement Structural effect Electron-Donating Group (EDG) Electron-Withdrawing Group (EWG) Inductive effect (sigma bond) Resonance effect (pi bond) Hyperconjugation Stability of system Acidity/Basicity of organic compound Electron delocalization Resonance structure (contributor) Hybrid structure Conjugated system Organic Chemistry Acids and Bases Organic Chemistry Acid Strength (pKa) Organic Chemistry Acid Strength (pKa) how to stabilize? Organic Chemistry Acids and Bases 1. 2. 3. 4. 5. 6. Charged species Electronegativity Size of atoms Hybridization effect Inductive effect Resonance Organic Chemistry Acids and Bases Organic Chemistry Acids and Bases Organic Chemistry Acids and Bases Organic Chemistry Predicting the Outcome of Acid-Base Reactions Organic Chemistry Predicting the Outcome of Acid-Base Reactions Organic Chemistry Predicting the Outcome of Acid-Base Reactions Circle the side favoured by equilibrium in the following acid-base reactions. The acidity of an organic compound can be evaluated on the basis of its pKa value (lower pKa means a stronger acid). (pKa: NH3 38, HCN 9, (CH3)3COH 17, acetone 20, PhNH3+ 4, H3O+ -1.7, CH3CH2CH2CH3 48, PhCH3 40). Organic Chemistry Inductive Effect • Inductive effect: the ability of a substituent to attract (electron withdrawing groups: EWG) or release (electron donating groups: EDG) electrons through sigma bonds because of its electronegativity. • Inductive effect: atom’s ability to polarize a covalent bond. Organic Chemistry Stabilization of a charged species: Electron Withdrawing or Donating Organic Chemistry Inductive Effect and Acidity Organic Chemistry Inductive Effect: Electron Movement along Sigma Bond Acid strength (pKa) Inductive effect weaken steadily as the distance from the substituent increases. Organic Chemistry Resonance Effect Resonance effect: electron (pi or lone pair) delocalization in conjugated systems. • Electron delocalization stabilizes ionic species or neutral molecules. (Dispersal of charge makes a species more stable). Resonance theory: • Molecule or ion are stabilized by resonance especially when the molecule or ion can be represented by two or more resonance structures of equal stability. • Resonance structures are useful because they allow us to describe molecules, radicals, or ions for which a single Lewis structure is inadequate. Organic Chemistry Electron Delocalization in Conjugated Systems Stability in organic acids Organic Chemistry Electron (p or Lone Pair) Delocalization in Conjugated Systems Stability in organic acids Organic Chemistry Electron (p or Lone Pair) Delocalization in Conjugated Systems Stability of organic species resonance structures (contributors) Organic Chemistry Conjugated Systems (a cumulated diene) Organic Chemistry Conjugated Systems Organic Chemistry Conjugated Systems Organic Chemistry Conjugated Systems: Higher Stability Organic Chemistry Conjugated Systems Why electrons can be delocalized in the p system? Organic Chemistry Conjugated Systems Which molecules are conjugated? Organic Chemistry Common Models of Conjugated Systems Common models of conjugated system and drawing resonances 1) 2) 3) 4) 5) 6) 1,3-butadiene Acrolein Vinyl chloride Allyl cation Allyl radical Allyl anion Organic Chemistry Rules for Drawing Resonance Structures 1 2 3 4 Organic Chemistry Curved Arrow Notation Graphical way to show movement of electrons (electron flow) during a reaction. Electrons move from a “source” (electron-rich) to a “sink” (electron-poor). Double(-headed) arrow is used for an electron pair. Fishhook arrow is used for a single electron. Organic Chemistry Resonance Structures Organic Chemistry Resonance Structures (Resonance Contributors) The delocalization of electrons leads to more than one possible arrangement of the electron pairs (pi electrons from double bonds or lone pairs) (the relative position of the atoms to each other is the same). Organic Chemistry Resonance and Stabilization Acidity of phenol: Although phenols are structurally similar to alcohols they are much stronger acids. The greater acidity of phenol owes to itself primarily to an electrical charge distribution in phenol. Organic Chemistry Drawing Resonance Structures Organic Chemistry Resonance and Geometry Organic Chemistry Resonance and Geometry Organic Chemistry Resonance and Reactive Centers Identify the reactive center for the nucleophilic attack in this reaction? Organic Chemistry Resonance and Reactive Centers Reaction Organic Chemistry Resonance Resonance. When more than one correct Lewis can be written for a molecule, each structure is a resonance form of the molecule. The presence of resonance forms means that the electrons are not localized between two nuclei but are delocalized over more than two nuclei. The result of electron delocalization is that electrons are attracted by a greater number of nuclei, which leads to a lower energy for the molecule and hence greater stability. Double-headed arrows () are used to indicate resonance forms. Draw all the possible resonance forms of compounds 1 and 2. Explain why compound 3 undergoes loss of bromide to produce a cation more easily than compound 4. Organic Chemistry Resonance Organic Chemistry Resonance 1) Draw and show resonance of the product of the following acid-base reaction of guanidine. 2) Why tetramethylguanidine is much a stronger base than dimethylacetamide? (Hint: use the stability of their conjugate acid). N,N- Organic Chemistry Resonance 1) Draw and show resonance of the product of the following acid-base reaction of guanidine. 2) Why tetramethylguanidine is much a stronger base than dimethylacetamide? (Hint: use the stability of their conjugate acid). N,N- Organic Chemistry Introduction to Organic Chemistry Isomerism Constitutional isomers Stereoisomers Optical activity and Optically active compounds Chiral molecules and achiral molecules Chirality Enantiomers and Diasteromers Z-E nomenclature CIP (Cahl-Ingold-Prelog) rule Organic Chemistry Important Terms and Concepts Isomerism (type of isomerism) Constitution and Structure 3D formula Configuration Conformation Enantiomer Racemic mixture Diastereomer Restricted rotation (Geometric isomer) Chirality (Optical isomer) Chiral center (stereocenter) Chiral molecule vs. Achiral molecule Organic Chemistry Isomerism/Stereochemistry Isomerism: different compounds have the same molecular formula. Constitutional isomer: atoms are connected in different order (different connectivity). Stereoisomer: constituent atoms are connected in the same sequence. Stereoisomers differ only in spartial arrangement. Stereochemistry: Study of the spatial characteristics of a molecule. Configuration: the arrangement of atoms in a molecule in space characterized by a particular stereoisomer. Stereoisomerism can arise from restricted rotation about double bonds or single bond of cycloalkanes (geometrical isomers) or from chirality (optical isomers). Organic Chemistry Isomerism Organic Chemistry Isomerism Organic Chemistry Summary of Different Kinds of Isomers Organic Chemistry Isomerism Organic Chemistry Constitutional Isomers Organic Chemistry Constitutional Isomers Organic Chemistry Constitutional Isomers Organic Chemistry Alkene Isomerism (Diastereomers) Geometric isomers: Isomers from structural rigidity (double bond or cycloalkane). Different properties Attention Organic Chemistry Alkene Isomerism (Diastereomers) Restricted rotation and the double bond Organic Chemistry Z-E Nomenclature Organic Chemistry Alkene Isomerism (Diastereomers) Organic Chemistry cis-trans Isomers Organic Chemistry Chiral Molecules (Optical Isomers) Organic Chemistry Stereoisomers Organic Chemistry Identification of Stereocencers Vinblastine is an anticancer agent used to treat cancer. - Circle and name all functional groups in vinblastine. List them as hydrocarbons, oxygen-containing, nitrogen-containing fuctional groups? - Mark all asymmetric carbons (Csp3 stereocenters) of vinblastine? - Show the hybridization states of some marked atoms? HO N CO2CH3 N N H H OCOCH3 H3CO CO2CH3 N H CH3 OH Organic Chemistry Stereocenter and Enantiomer Study the relationship between object and its mirror image. Organic Chemistry Stereocenter and Enantiomer Organic Chemistry Chiral Molecules and Enantiomers Chiral molecule mirror mirror image 3D molecule = object non-superimposable mirror plane of symmetry plane of symmetry Achiral molecule superimposable Organic Chemistry Chiral Molecules and Achiral Molecules Organic Chemistry Chiral Molecules and Plane of Symmetry Organic Chemistry Chiral Molecules and Optically Active Molecules Optically Active Molecules • A beam of ordinary light consists of electromagnetic waves that oscillate in an infinite number of planes. When a beam of ordinary light passes through a polarizer, only the light waves oscillating in an single plane pass through and the light is said to be plane-polarized. • When a beam of plane-polarized light passes through a solution of certain organic molecules, such as sugar and camphor, the plane of polarization is rotated. Organic molecules that exhibit this property are said to be optically active. Organic Chemistry Polarimeter and Chiral Molecules Organic Chemistry Polarimeter and Chiral Molecules Specific rotation t Organic Chemistry Specific Rotation Organic Chemistry Chiral Molecules and Enantiomers Optical rotation Organic Chemistry Enantiomers and Biological Activities Organic Chemistry R-S Nomenclature of Enantiomers Assignment of priorities: CIP rules (Cahn-Ingold-Prelog) Organic Chemistry R-S Nomenclature of Enantiomers R-S system for naming absolute configuration Organic Chemistry R-S Nomenclature of Enantiomers 1. 2. 3. 4. Finding chirality One stereocenter = two enantiomers, one is R and the other S. Assign priorities in order of decreasing atomic number. Apply the first point of difference rule. Orienting the molecule so that the lowest priority group is pointing back, away from us. Assign the stereochemical configuration. Organic Chemistry R-S Nomenclature of Enantiomers Determine whether the following pairs of structures are identical or constitutional isomers? Give R-S configurations of the following pairs and identify relationships of compounds? Organic Chemistry Fischer Projection Formula Organic Chemistry 2D Fischer Projection Formula Organic Chemistry Compounds with More than One Stereocenters Organic Chemistry Compounds with More than One Stereocenters Two stereocenters, four possible stereoisomers Fischer projection? Enantiomers or Diastereomers? Organic Chemistry Compounds with More than One Stereocenters Organic Chemistry Compounds with More than One Stereocenters Organic Chemistry Chiral Molecules and Chirality Organic Chemistry Achiral Meso Compounds Organic Chemistry Achiral Meso Compounds Organic Chemistry Cyclic Compounds with More than One Stereocenters Organic Chemistry Compounds with More than One Stereocenters H OH HO H HO H OH HO H H H H OH HO OH H Organic Chemistry Classification of Organic Reactions Classification of organic reactions Heterolytic bond cleavage Homolytic bond cleavage Structures of reactive intermediates Reagents: Nucleophiles and Electrophiles Mechanisms and main FG reaction mechanisms Polar (ionic) reactions and Radical reactions Organic Chemistry Important Terms and Concepts Organic reaction Reaction mechanism Arrow pushing technique Polar reaction – ionic mechanism Radical reaction – radical mechanism Heterolytic bond cleavage Homolytic bond cleavage Carbocation Free radical Carbanion Reagent Nucleophile Electrophile Energy diagram Transition state Reactive intermediate Organic Chemistry Classification of Organic Reactions Addition (A) Elimination (E) Organic Chemistry Classification of Organic Reactions Substitution (S) Rearrangement Organic Chemistry I Mechanism of Organic Reactions by Organic Chemistry I Homolytic Bond Breaking Radical reaction Organic Chemistry I Radical Reactions Organic Chemistry I Heterolytic Bond Breaking bond polarization Polar (Ionic) reaction Organic Chemistry I Heterolytic Bond Breaking Organic Chemistry I Structures of Reactive Carbon Intermediates 6e 8e methyl cation Carbocation methyl anion Carbanion 7e Carbocations and radicals are electron deficient, while carbanions are electron rich. methyl radical Organic Chemistry I Stability of Reactive Carbon Intermediates Organic Chemistry I Stability of Reactive Carbon Intermediates Example: Arrange the stability order of the following radicals or carbocations? Organic Chemistry Polar Reactions: Reagents in Reactions Electrophiles and Nucleophiles Organic Chemistry Polar Reactions: Nucleophiles and Electrophiles Organic Chemistry Polar Reactions: Nucleophiles and Electrophiles Organic Chemistry Reactions, Mechanisms, and FGIs Functional Group Interconversion (FGI) 1) Radical Substitution SR (alkane) 2) Electrophilic Addition AE (alkene, alkyne) 3) Radical addition AR (alkene, alkyne) 4) Electrophilic Substitution SE (arene) 5) Ncleophilic Substitution SN (alkyl halide) 6) Elimination E (alkyl halide, alcohol) 7) Nucleophilic Addition AN (aldehyde, ketone) 8) Nucleophilic Addition AN – Elimination of Leaving Group (LG) (carboxylic acid and derivatives – acyl compounds) Organic Chemistry Reactions, Mechanisms, and FGIs Organic Chemistry Polar Reactions nucleophile starting materials (reactants) electrophile products Organic Chemistry Mechanism, Energy Diagram, Transition State and Reactive Intermediates Organic Chemistry Mechanism, Energy Diagram, Transition State and Reactive Intermediates Organic Chemistry Topics of Review 1 Organic Chemistry I Review 1 (50') Class: Student: Major: Date - Month - Year: Review topics: 1) Functional Groups and Hybridization (shapes of organic molecules) 2) Intermolecular interactions: Hydrogen bonding 3) Isomerism (Z-E and R-S configuration, stereochemical relationship) 4) Electronic effects (Inductive (acidity) and Resonance effects (stability and charge separation) 5) Representation of organic compounds (Lewis, dash, bond-line formula, 3D formula, Fischer projection formula) 6) Nucleophile and electrophile in polar reactions 7) Reaction mechanisms
