topic 1:structure, bonding and hybridization in organic molecules 1.1atomic structure of...
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Topic 1:Structure, Bonding and Hybridization in Organic Molecules
• 1.1 Atomic Structure of Carbon– Orbital Shapes
• Atomic Orbitals s, p
– Hybridization• Formation of sp3, sp2, sp orbitals
• 1.2 Bonding in Organic Molecules– Bonding and antibonding orbitals– Overlap of hybridized orbitals to form sigma () and pi (
bonds– Comparison of bonding in alkanes, alkenes and alkynes– Bonding in ethane, ethylene, acetylene
Topic 2: Molecular Properties and Molecular Models
– Molecular Modeling of Organic Molecules• Ball and stick model• Space-filling model
– Molecular Dynamics– Visualization Aids
• Molecular models
– Comparison of 3D and 2D structures
Topic 3: Nature of Organic Compounds
• 3.1Functional Groups
– C skeleton (C-C, C-H Framework)
– Heteroatoms and Bonds-
• Alkenes, alkynes, haloalkanes, acyl halides, alcohols, ethers, aldehydes, ketones, carboxylic acids and carboxylic acid derivatives, amines and amides
• 3.2Alkyl Groups– Nomenclature: Common names and systematic IUPAC names
– Alkyl Groups (R groups)
• Methyl, ethyl, propyl, n-butyl, isopropyl, isobutyl, sec-butyl, tert-butyl, neopentyl
– Classification of Alkyl Carbons• Primary (1o), Secondary (2o), Tertiary (3o), Quartenary (4o)
Topic 4: Structure and Conformations of Alkanes and Cycloalkanes
• 4.1Conformations of Ethane– 3D Visualization – Newman Projections - eclipsed, staggered conformations– Energy profile diagrams of bond rotations
• 4.2Conformations of Butane– Antiperiplanar conformation, Synperiplanar conformation,
Gauche conformation– Rotational Barriers– Newman Projections– Energy profile diagrams of bond rotations
Topic 4: Structure and Conformations of Alkanes and Cycloalkanes.
• 4.3 Cycloalkane Structure and Conformations– Cyclopropane
• Angle strain• Ring strain
– Cyclobutane• Puckered conformation, dynamics of rotations
– Cyclopentane• Envelope conformation, dynamics of rotations
– Cyclohexane• Chair conformation
– Cycloheptane• Bicyclic alkanes, cis- and trans- decalin
– Norbornane– Steroid Nuclues
Topic 4: Structure and Conformations of Alkanes and Cycloalkanes contd.
• 4.4Conformation of Cyclohexanes– Chair Conformations
• Axial substituents and Equatorial substituents• Newman projection• Gauche interactions
– Boat Conformations• Flagpole, transannular interactions
– Twist-boat Conformation• Dynamic conformer changes• Relief of torsional and flagpole strain
– Comparison of energy of cyclohexane conformations– Monosubstituted cyclohexanes
• Chair, half chair, boat• Ring flips• Comparison of steric effects of different substituents (1,3-diaxial interactions)
– Calculation and comparison of G for conformational changes
Topic 5: Reactions of Alkenes
• 5.1 Reduction of Alkenes– Heterogeneous Catalysis– Hydrogenation Mechanism– Stereochemistry of Addition
• Stereospecific syn addition of hydrogen• Addition to prochiral faces to form
enantiomers• Worked examples of syn additions
Topic 5: Reactions of Alkenes contd.
• 5.2Bromination of Alkenes– Addition of Bromine in CCl4 to Bonds
– Stereochemistry of Bromine Addition
– Anti-Addition Mechanism– Bromonium ion formation– Arrow notation – Antiperiplanar conformation resulting from
stereospecific anti addition– Determining resultant product stereochemistry
– Regioselectivity (addition of competing nucleophiles and formation of regioisomers)
– Steric and Electronic Factors Affecting Regioselectivity
Topic 5: Reactions of Alkenes contd.
• 5.3Hydroxylation of Alkenes– Stereospecific Hydroxyl Additions– Syn-Hydroxylation Forming cis-Diols in Cyclic Systems
– Syn-Addition Mechanism
– Syn addition of hydroxyls via permanganate ion esters– Arrow notation– Synperiplanar conformation of product– Resultant product stereochemistry-enantiomers, meso etc.
– Anti-Hydroxylation to form trans-Diols in Cyclic Systems• Epoxide ring opening Mechanism
– Epoxidation by peroxides– Addition of nucleophiles to epoxides– Antiperiplanar conformation of product
– Worked Examples
Topic 6: Alkynes of Reactions
• Alkyne Hydration• Acid catalyzed hydrolysis
– H2SO4, Hg2+
• Hydroboration-oxidation
– Disiamyl borohydride
– Pi Orbital Structure of Alkynes– Regioselectivity of Electrophile Attack
• H+ addition vs boron electrophile addition
– Hydration and Enol formation mechanism• Hydroboration, peroxide oxidation, hydrolysis, tautomerization
– Arrow Notations– Comparison of Regioselectivity of the Electrophiles– Worked Examples
Topic 7: Streochemistry
• 7.1Introduction to Stereochemistry– Stereogenic Carbons/Stereocenters– Enantiomers
• Non-superimposable mirror images• Chirality• Cahn-Ingold-Prelog R,S nomenclature for determination of absolute
configuration– Fischer projections
• 7.2Multiple Stereocenters– Classification of isomers– Diastereomers– Enantiomers– Calculation of maximum number of possible stereoisomers– Stereochemistry in Cyclic Compounds
• Cis and trans diastereomers, meso diastereomer• Alkene diastereomers• Stereogenic centers in taxol
– Worked examples
Topic 7: Streochemistry contd.
• 7.3Biochemical Roles of Enantiomers– Stereoselective substrate binding– Enzyme binding– Iboprofen– Thalidomide– Morphine– Levorphanol– Dextrorphan
Topic 8: Alkyl halides: Free radical reactions and Organometallic compounds
• 8.1Free Radical Halogenation– Halogenation of Methane
• Initiation mechanism
• Propagation mechanism
• Termination mechanism
– Arrow Notation– Chain Reactions– Worked examples
Topic 8: Alkyl halides: Free radical reactions and Organometallic compounds contd.
• 8.2Reactions of Organometallic Compounds– Reverse polarity on carbon in organometallic compounds– Organolithium reagents
• Tight-ion pairs• Basicity and nucleophilicity of alkyl anions• Basic character• Nucleophilic ability of carbanions
– Grignard Reagents• Nucleophilic addition mechanism• Formation of alcohols via Grignards• Arrow notations
– Dialkyl Cuprates• Substitutions with alkyl halides
– Worked Examples
Topic 9: Nucleophilic Substitution Reactions and Elimination Reactions, (SN1, SN2, E1, E2)
• 9.1The SN2 Reaction
• Kinetics and stereochemistry data
• Inversion of configuration
– SN2 Reaction Mechanism
• Backside attack
• Change in hybridization
• Leaving groups
• Change in relative configuration (R or S)
• Arrow notation of concerted reactions
– Reaction Profile Energy Diagram
– Worked examples
Topic 9: Nucleophilic Substitution Reactions and Elimination Reactions, (SN1, SN2, E1, E2) contd.
• 9.2The SN1 Reaction
– Unimolecular nucleophilic substitution– Solvolysis of alkyl halides– Formation of carbocations– Racemization– Solvolysis Mechanism
• Arrow notation• Hybridization changes• Formation of achiral carbocation intermediate• Pro-R face, pro-S face
– Reaction profile energy diagram– Worked Examples
Topic 9: Nucleophilic Substitution Reactions and Elimination Reactions, (SN1, SN2, E1, E2) contd.
• 9.3Steric Factors in Nucleophilic Substitutions
– Influence of steric factors involving -C on SN1 vs SN2
– Primary, secondary, and tertiary alkyl halides– Factors promoting backside attack vs carbocation
formation – carbon branching and rotation of branched substituents– Steric hindrance due to nucleophile
– Worked examples
Topic 9: Nucleophilic Substitution Reactions and Elimination Reactions, (SN1, SN2, E1, E2) contd.
• 9.4E2: Bimolecular Eliminations– Formation of alkenes– Rate expression– Bases used for eliminations– Stereoselective Elimination Mechanism
• Trans vs cis alkene formation• Concerted reactions• Hybridization changes
– Arrow notation – Newman projections illustrating stereoselectivity
• 9.5E1: Unimolecular Eliminations– Elimination Reaction Mechanism– Protic solvents and solvent assistance to
• Ionization• Stabilization of carbocations via solvation
– Worked examples
Topic 10: Conjugated Systems
• 10.1ConjugatedSytem – Localized and Delocalized Systems– Orbital Diagrams
• Bonding, HOMO orbitals• Antibonding LUMO orbitals• Transitions *
– Allyl Systems• Cation, anion, radical allyl systems• Molecular orbital diagrams• Bonding orbitals
• Non-bonding orbitals 2
• Antibonding orbitals
• Nodal planes and electron density distribution– Butadiene
• Bonding and antibonding orbitals• Nodal planes and electron distribution• Coplanar s-cis, s-trans dienes
– Octatetraene– Summary Energy Diagram of Conjugated systems– Absorption of electromagnetic radiation UV-Vis
range
Topic 10: Conjugated Systems contd.
• 10.2The Diels-Alder Reaction– [4+2] Cycloaddition
• Rotation of s-cis to s-trans of diene
– Diene-dieneophile interaction mechanism– HOMO-LUMO interactions
– Hybridization changes
• Overlapping of Frontier Orbitals
• Effect of electron withdrawing groups and electron donating groups on Diels-Alder reaction
• Stereochemistry of product
• Endo vs exo orientation and secondary orbital interactions
• Kinetic vs thermodynamic product control
• Stereochemistry of products– Formation of enantiomers, diastereomers
Topic 11: Benzene and Aromaticity
• Benzene and Aromatic Compounds• Ball and stick and space-filling models
– Aromaticity• Planar, cyclic• Conjugated• (4n+2) pi electrons (Huckel’s Rule)
– Orbital Diagrams• Bonding, antibonding orbitals, nodal planes, e distribution, energy
levels– Application of Huckel’s Rule to
• Monocyclic systems and polycyclic aromatic systems– Annulenes– Aromatic Heterocycles
• Furan, pyridine, indole (hybridization)– Aromatic Ions
• Cyclopropenyl, cyclopentadienyl, tropylium cations
– Application of Huckel’s Rule to• Non-aromatic systems, Anti-aromatic systems• [10]-Annulene
Topic 12: Electrophilic Aromatic Substitution Reactions
• 12.1Electrophilic Aromatic Substitution• Electrophilic Aromatic Substitution Mechanism
• Electrophile attack• Arenium ion - complex• Resonance stabilization• Removal of proton and regaining aromaticity
– Reaction profile energy diagram– Examples of electrophiles
Topic 12: Electrophilic Aromatic Substitution Reactions contd.
• 12.2Substituent Effects in EAS– Reactivity and regioselectivity
• Reaction profile energy diagram cf. Rates of activators vs deactivators
• Resonance in phenol• Resonance in benzaldehyde
– Directing Effects of Substituents on di- and poly-Substitutions• Hammond's postulate• Distribution of charges on substituted benzenes• Steric effects• bromination of toluene mechanism• Bromination of nitrobenzene• Relationship between relative reactivity and regioselectivity
– Worked examples
Topic 13: Ethers
• Cyclic Polyethers– Structures and models of cyclic polyethers– Size exclusion-ion-chelation– Selective ion binding– Applications in industry
Topic 14: Reactions of Aldehydes and Ketones
• 14.1 Aldehydes and Ketones– Structure of carbonyl group– Orbital diagrams
• Polarity• Nucleophile-electrophile sites of interactions
– Nomenclature examples– Dynamics of axial and equatorial addition to cyclohexanone– Nucleophile addition Mechanism
– Tetrahedral intermediates– Comparison of oxygen nucleophiles, OH2, ROH, RO-
– Comparison of nitrogen nucleophiles, NH3, NH2R, NH2-
– Comparison of carbon nucleophiles RMgX, RLi, CN-
– Hydrides LiAlH4, NaBH4
• Asymmetric induction– Addition of cyanide - Cram’s rule
• Worked Examples
Topic 14: Reactions of Aldehydes and Ketones contd.
• 14.2Tautomerization– Acid catalyzed tautomerization mechanism
• Enol formation• Keto-enol tautomers
– Enol tautomers in• Phenols• B-Diketones• Thymines• Imidazole
Topic 14: Reactions of Aldehydes and Ketones contd.
• 14.3 Hemiacetal-Acetal Formation• Hemiacetal formation mechanism
• Protonation of carbonyl, resonance forms• Nucleophile attack -• Tetrahedral intermediate• Deprotonation - protonation
– Acetal formation mechanism• Dehydration• Formation of methoxy cations
– Acetals and Hemiacetals Hydrolysis– Reversibility of acetal reaction mechanisms
– Acetal to aldehyde
Topic 14: Reactions of Aldehydes and Ketones contd.
• 14.4Aldol Reaction– Enolate formation mechanism– Resonance stabilized enolate ion formation
• Removal of -C-H proton• Condensation Reactions
– Arrow notation– Stereochemistry of aldol reactions
• Pro-R Face• Pro-S Face
Topic 15: Carboxylic Acids and Derivatives
• 15.1Carboxylic Acids and Derivatives– Acidity of carboxylic acids– Modeling of acyl groups
• Acyl chloride, • Cyclic and acyclic acid anhydride• Esters and Lactones• Amides -primary/secondary/tertiary acyclic and cyclic (lactams)• Nitriles
– Relative reactivity of derivatives• Conversion of more reactive to less reactive derivative
– Nucleophilic acyl substitution mechanism– Examples of Nucleophilic Acyl Substitutions
• Base hydrolysis• Addition of Grignards• Amide hydrolysis
Topic 15: Carboxylic Acids and Derivatives contd.
• 15.2 Methanolysis of Acetyl Chloride– Nucleophilic acyl substitution mechanism
– Influence of leaving group– Addition of nucleophile to Carbonyl– Tetrahedral intermediate formation– Deprotonation– Internal nucleophilic displacement of
leaving group• Arrow notation of reactions
Topic 16: Polymers
• 16.1Introduction to Polymers– Monomers– Polymers
• Backbone• Side chains
– Tacticity• Stereochemistry of substituents• Relative and absolute configuration
– Syndiotactic (R,S alternating)– Isotactic (all R or all S)– Atactic (R and S random)
• Illustration of tacticity with– Polyethylene polymers (no tacticity)– Polypropylene polymers– Recycling
Topic 16: Polymers contd.
• 16.2 Survey of polymers– Addition Polymers
• Addition to pi bonds– PVC, Teflon, polystyrene, polymethacrylate
• Macroscopic properties– Crystalline (HDPE)– Amorphous– Random conformation
• 3-D space-filling modeling of PVC, Teflon, styrene, polymethacrylate
• Uses of polymers
– Condensation Polymers• Co-polymers• Formation of condensation polymers• PET (polyethyleneterephthalate)• Nylon (6,6)• Worked examples
Topic 17: Amines
• Amines: Structure and Properties– Primary, secondary, tertiary, and quaternary amines– Models illustrating
• Hybridization of N in– Alkylamines– Enamines– Arylamines
– Model of diazonium salt– Models of N-heterocyclic systems
• Pyrrolidine, pyridine, indole, imidazole• Alkaloid example - cocaine
– Inversion at N and hybridization changes– Basicity of amines
• Protonation mechanism
• Comparison of pKb of
• Alkylamines, ammonia, arylamines
Topic 18: Carbohydrates
• 18.1 Monosaccharides– Aldoses– Stereochemistry of 3C, 4C, 5C and 6C aldoses– Relative configurations
• D, L-Stereoisomers• Fischer projections• Enantiomers• Diastereomers
– Epimers
– Internal cyclizations• Arrow notations• Haworth projections• Anomeric centers
– Relative stereochemistry of anomers• Furanose and pyranose hemiacetals• Interconversion/mutarotation• 3D Models of carbohydrates
Topic 18: Carbohydrates contd.
• 18.2Disaccharides and Polysaccharides– Disaccharides
• Glycosidic linkages• Reducing and non-reducing disaccharides• Glycosidic linkages and 3 D structures of
– Cellobiose – Sucrose– Maltose
– Polysaccharides• 3 D Models illustrating assembly and H-bonding in
– Linear polymers» cellulose
– Helical/curved polymers» Amylose, details of 12-mer-helix
– Branched polymers» Amylopectin
– Shape - function relationship
Topic 18: Carbohydrates contd.
• 18.3 Applications of Carbohydrate Polymers
– Cyclodextrin Roxatanes
– Formation of polymeric nanotubes
• 3D Modeling of– -cyclodextrin– -cyclodextrin
• 3D Modeling of Roxatanes– Polyethylenoxy bisamine– Barbell shaped molecules with stoppers
• Cyclodextrin roxatanes– Formation of molecular necklace– Covalent linking to form nanotubes/pores
Topic 18: Carbohydrates contd.
• 18.4 Anti-inflammatory Agents– Sialyl Lewisx
• 3D modeling of the structure• Cell adhesion and anti-inflammatory response
– Cytokines– Leukocytes-selectin adhesions
• Repair of injury by leukocytes• Inflammation blocking-potential use of Sialyl
Lewisx
Topic 19: Proteins
• 19.1Amino Acids and the Peptide bond• Classification of amino acids with regard to the side chains
– Models of polar, non-polar, acidic, basic and neutral amino acids
• Stereochemistry, L-amino acids– Zwitterions
– Peptide Bond• Details of peptide bond geometry
– Restricted rotation, plane of peptide bonds
• C-terminus and N-terminus of polypeptide• Modeling of conformation
– Peptide bond conformations, Side chain conformations
– Protein organization• Secondary structures (alpha helix and beta pleated)• Tertiary structures
Topic 19: Proteins contd.
• 19.2Beta pleated Sheet• -strand ex. Polyvaline• 2D and 3D modeling
– Details of linear and stacked chain» Top view, side view and end view
• H-bonding fit• Parallel and anti-parallel orientation• 3D Modeling of silk polymer
• 19.3Alpha helix• 3D modeling of coiled backbone illustrating
– Right handed helix– Side chain positions– H-bonding– Net dipole
– Comparison of -helix and 310 helix
Topic 19: Proteins contd.
• 19.4 Protein Organization– Io-IVo structures– Peptide linkages– Covalent crosslinking– Supersecondary structures
• Folding motifs• Topological diagrams and 2D and 3D models of
– -turn- hairpin turns and plane of peptide bonds
– -turn-, -turn-, other turns, -meander etc. – Tertiary structures
• Globular proteins– Bacteriorodopsin
– Quaternary structures• Non-covalent aggregates of dimers, tetramers, hexamer
Topic 20: Lipids
• 20.1Classification of Lipids– Steroids: Models illustrating
• Rings A-D, 5, 5• Cortisone
• Lanosterol formation from squalene– Epoxide formation, cascading
– Terpenes– Isoprene units– Head-tail linkages
• Limonene, vitamin A
– Prostaglandins
– Models of PGE2
– Arachidonic acid to prostaglandin
Topic 20: Lipids contd.
• Fats and Oils• Triacylglycerols
• Hydrolysis
– Saturated fatty acids
– Unsaturated fatty acids
• Phospholipids• Chemistry of polar heads, nonpolar chains
– Cephalins
– Lecithins
– Phosphatidyl serine
– Phosphatidyl choline
» Neurotransmitters, emulsifier, LDL
– Stacking of phospholipids in membrane bilayer
– Worked examples
Topic 20: Lipids contd.
• 20.2Nutrition Labeling and Organic Compounds– Nutrition facts on Fat
• Fatty acids, triacylglycerides– Nutrition facts on Cholesterol– Nutrition facts on Carbohydrates
• Sugars• Starch vs cellulose
Topic 21: Nucleic Acids
• 21.1 Structure of Heterocycles– Oxygen heterocycles– Sulfur heterocycles– Nitrogen heterocycles– Aromatic nitrogen heterocycles
• Purines, pyrimidines
– Macrocyclic nitrogen heterocycles• Phophines• Drugs for aids
– AZT, ddI• Stimulants• Neurotransmitters• Antibiotics
– Penicillins, keflex pulvule, cefotetan, toradol• Antinausea agents
– Scopalamine• Antiviral agents
– Ribavirin, acylclovir
Topic 21:Nucleic Acids contd.
• 21.2Components of DNA– Bases
• Purines, pyrimidines• H-bonding-donor, acceptor sites• Linkage to sugar
– Sugars• 2-deoxy ribose
– Endo conformation in B-DNA– Nucleosides
• Anti-syn conformation for purines and pyrimidines– Nucleotides: 3D modeling of
• Mononucleotides• Dinucleotides 5’-3’ phosphodiester linkage
– Base pairing• Details of conformations of base pairs
– A-T, G-C pairing– Major groove, minor groove– H-donor-acceptor sites in grooves– Stacking of nucleotides
Topic 21: Nucleic Acids contd.
• 21.3 DNA Macrostructure– 3D solid and wire modeling illustrating
• Pitch (turn)• Diameter• Backbone• Bases• Inclination• Propeller twist• Major and minor Grooves
– DNA binding agents: 3D Modeling of• Antibiotic Lexitropsin binding in minor groove
• 21.4 Self-Replicating Synthetic Molecules – Mechanism of formation of complementary strand on template– Synthetic mutants
Topic 22: Electrocyclic Reactions
• Pericyclic Reactions– Concerted mechanism– Cyclic transition state– Interconversion of bonds
– Electrocyclic Reactions– MO diagrams– Thermal reactions (HOMO)– Photochemical reactions (LUMO)
– Thermal and photochemical 4n and [4n+ 2] electron systems ring closure– MO diagram of butadiene hexatriene– Thermal photochemical ring closures– Stereochemistry of ring closure– Conrototory vs disrototory
– Woodward-Hoffman Rules– Cycloadditions- Go to Int. Mod. 10 for Diels Alder Reaction
Topic 23: Special Topics
- Special Topic: Host -Guest chemistry• Carcerand-carceplex (irreversible) • hemicarcerand-hemicarceplex (reversible)
Topic 24: Self Tests
• Self Test 1
• Self Test 2