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