M.Sc.

II (ORGANIC CHEMISTRY) REVISED SYLLABUS-2009

SEMESTER - III CH -350: CH -351: CH -352: CH 353: ORGANIC REACTION MECHANISM SPECTROSCOPIC METHODS IN STRUCTURE DETERMINATION ORGANIC STEREOCHEMISTRY FREE RADICALS, PHOTOCHEMISTRY PERICYCLIC REACTIONS AND THEIR APPLICATIONS

SEMESTER IV CH - 450: CH- 451: CH- 452: CHEMSITRY OF NATURAL PRODUCTS SYNTHETIC METHODS IN ORGANIC CHEMISTRY HETEROCYCLIC CHEMISTRY, CHIRON APPROACH & MEDICINAL CHEMISTRY

PRACTICAL COURSES CH - 347: CH- 447: CH - 448: TERNARY MIXTURE SEPARATION SINGLE STAGE AND TWO STAGE PREPARATIONS PROJECT AND PRACTICALS:

M.Sc.II (ORGANIC CHEMISTRY) REVISED SYLLABUS-2009 SEMESTER - III CH - 350 ORGANIC REACTION MECHANISM (60L

1.

Carbanions - Formation, stability and mechanisms of important reactions. Enamines-formation and applications Ref. 1, 2, 3 and 7

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2.

Reactions of carbenes and nitrenes. Ref. 7 and relevant pages from 8

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3.

Neighbouring group participation Ref. 1 4. Ester hydrolysis (acid and base catalysed) Ref. 1 5. Kinetic and non-kinetic methods used for determination of reaction mechanism. Ref. 1 6. Hammett equation and its applications. Linear free energy relationship Ref. 1, 3, 4, 5, 6 7. Mechanisms in biological chemistry Ref. 7 pp 1381-1412

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Books: 1. Mechanism and structure in Organic Chemistry E. S. Gould (Holt, Rinehart and Winston) 2. Advanced organic chemistry by J. March, 6 Ed. 3. Advanced organic chemistry part-A. F. A. Carey and R. J. Sundberg, 5 Ed. Springer (2007) 4. Physical Organic chemistry J. Hine 5. A guidebook to mechanism in organic chemistry Peter Sykes 6 Ed. Orient Longman 6. The Hammett equation C. D. Johnson, Cambridge University Press (1973) 7. Organic Chemistry J. Clayden, N. Greeves, S. Warren and P. Wothers. Oxford University Press (2001) 8. Michael P. Doyle and David C. Forebes, Chem. Rev. 98, 911-935 (1998)
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CH- 351 SPECTROSCOPIC METHODS IN STRUCTURE DETERMINATION 1. Recapitulation of UV, IR and H NMR. 2.
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H NMR (Advanced ideas) FT techniques, Spin Coupling, Ramsay mechanism of spin

coupling, different spin systems (AB, AM, AX, AMX systems, calculation of line intensities and chemical shifts), factors affecting coupling constants, rate processes. Different types of coupling. Methods used for simplification of PMR spectra. NOE, spin decoupling. Two

dimensional (2D) NMR Techniques (DEPT with 3 different angles, COSY, HETCOR). Medical application of PMR 3.
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C NMR elementary ideas, instrumental problems, chemical shift features of hydrocarbons,

effect of substituents on chemical shifts, different type of carbons (Alkene, alkyne, allene and carbonyl) (12)

4. Mass Spectrometry Theory, instrumentation, various methods of ionisation (field ionisation, SIMS, FAB, MALDI, Californium plasma), different detectors (magnetic analyzer, ion cyclotron analyzer, Quadrupoule mass filter) time of flight (TOF). Rules of fragmentation of different functional groups, factors controlling fragmentation. 5. Problems based on joint application of UV, IR, PMR, CMR, and Mass. (Including reaction sequences) Ref.9 Books: 1. Introduction to Spectroscopy D. L. Pavia, G.M. Lampman, G. S. Kriz, 3 college publishers). 2. Spectrometric identification of organic compounds R. M. Silverstein, F. X. Webster, 6 Ed. John Wiley and Sons. 3. Spectroscopic methods in organic chemistry - D. H. Williams and I. Flemming Mc Graw Hill 4. Absorption spectroscopy of organic molecules V. M. Parikh 5. Nuclear Magnetic Resonance Basic Principles- Atta-Ur-Rehman, Springer-Verlag (1986). 6. One and Two dimensional NMR Spectroscopy Atta-Ur-Rehman, Elsevier (1989). 7. Organic structure Analysis- Phillip Crews, Rodriguez, Jaspars, Oxford University Press (1998)
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Ed. (Harcourt

8. Organic structural Spectroscopy- Joseph B.Lambert, Shurvell, Lightner, Cooks, Prentice-Hall (1998). 9. Organic structures from spectra Field L.D., Kalman J.R. and Sternhell S. 4 Ed. John Wiley and sons Ltd.
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CH 352 ORGANIC STEREOCHEMISTRY 1. Stereochemistry of six membered rings and reactions thereof. Ref. 1, 6, 7 2. Stereochemistry of rings other than six membered Ref. 1, 6, 7 3. Fused Bridged and caged rings Ref. 1, 2, 6, 7 4. Resolution of racemic modification Ref. 1, 6, 7 5. Recapitulation of prochirality, homotopic and heterotopic ligands, stereoselectivity in cyclic compounds, enantioselectivity, diastereoselectivity, stereoselective aldol reactions. Crams rule, Felkin Anh rule, Crams chelate model. Asymmetric synthesis use of chiral auxiliaries, chiral reagents and catalysts, asymmetric hydrogenation, asymmetric epoxidation and asymmetric dihydroxylation. Ref. 3 chapters 33, 34, 35 6. Stereochemistry of Morphine, Quinine and Lactone Fusion in Enhydrin including principles of ORD ,CD Ref. 4, 5, 6 (10) (20) (07) (10) (05) (60L) (08)

Books: 1. Stereochemistry of carbon compounds - E. L. Eliel 2. Stereochemistry of carbon compounds - E. L. Eliel and S. H. Wilen 3. Organic Chemistry J. Clayden, N. Greeves, S. Warren and P. Wothers (Oxford Press.) 4. Chemistry of Natural Products N. R. Krishnaswamy (University Press) 5. Organic Chemistry vol. II - I. L. Finar, 5 edition (Longman) 6. Stereochemistry of organic compounds Nasipuri 7. Stereochemistry of organic compounds-Kalsi 8. Organic stereochemistry - JagdambaSingh
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CH 353 FREE RADICALS, PHOTOCHEMISTRY PERICYCLIC REACTIONS AND THEIR APPLICATIONS 1. Formation, stability and detection of long and short-lived radicals. Homolysis and free radical displacement, addition and rearrangements, Radical cyclisation in synthesis. Ref. 1, 2, 3 2. Photochemistry general principles, photochemistry of carbonyl compounds, aromatic compounds, alkenes and dienes. Ref. 2, 4 3. Pericyclic reactions Analysis (correlation diagrams, FMO approach, ATS concept) and examples of electrocyclic, cycloaddition, sigmatropic reactions and ene reactions. Ref. 2, 5, 6, 7 4. Application of photochemical reactions in synthesis Isocomene, Cedrene, Ladderane and Vitamin D3, Ref. 8, 9, 10, 11, 12,13 5. Application of Pericyclic reactions in synthesis Endiandric acids A D. Ref. 8 Books/References: 1. Mechanism and structure in Organic Chemistry E. S. Gould (Holt, Rinehart and Winston) 2. Advanced Organic Chemistry, Part A F. A. Carey and R. J. Sundberg, 5 Ed. Springer (2007). 3. Radicals in Organic Synthesis B. Giese, Pergamon press (1986) 4. a) Organic photochemistry: A visual approach-Jan Kopecky, VCH publishers (1992).
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b) Excited states in Organic Chemistry- J.A. Barltrop and J.D.Coyle, John Wiley & sons 5. Conservation of orbital symmetry R. B. Woodward and R. Hoffmann; Verlag chemie, weinheim (1970).

6. Orbital Symmetry : A problem solving approach- R. E. Lehr and A. P. Marchand; Academic (1972). 7. Organic reactions and orbital symmetry, 2 University Press. 8. Classics in total synthesis- K. C. Nicolaou and E. J. Sorensen; VHC (1996) 9. P. A. Wender and J. J. Howbert J. Am. Chem. Soc. 103, 688-690 (1981) 10. Henning Hopf et al Eur. J. Org. Chem., 567-581, (2005) and references cited therein. 11. G.Mehta, M.B.Viswanath et al Angew Chem, 104, 1557-1558 (1992) and references cited therein 12. D.H.R. Barton et al J. Am. Chem. Soc. 95(8), 2748-2749 (1973). 13. Henning Hopf, Angew.Chem.Int.Ed. 42, 2822-2825 (2003).
nd

Ed. T. L. Gilchrist and R. C. Storr; Cambridge

SEMESTER IV CH - 450 CHEMSITRY OF NATURAL PRODUCTS 1. Structure , stereochemistry and biogenesis of Hardwickiic acid, Camptothecin and Podophyllotoxin Ref. 1 to 4 and 11 2. Synthesis of i) Reserpine (Woodward synthesis) ii) Taxol iii) Estrone and Mifepristone iv) Strychnine (Overmans synthesis) v) Fredericamycin A Ref. 5,6 Ref. 6 Ref. 6,7 Ref. 6 Ref. 5 (30) (20) (10) (60L)

3. Biogenesis The building blocks and construction mechanism of 1. Terpenoids Mono, Sesqui, Di and Triterpenoids and cholesterol 2. Alkaloids derived from ornithine, lysine, nicotinic acid, tyrosine and tryptophan.

3. The shikimate pathway cinnamic acids, lignans and lignin, coumarins, flavonoids and stilbens, isoflavanoids and terpenoid quinones. Ref. 8, 9, 10 Books/References: 1. J. Am Chem. Soc. 88, 3888 (1966). 2. M. C. Wani and M. E. Wall J. Org. Chem. 34, 1364 (1969). 3. (i) Tetrahedron Letters, 3751 (1964)., (ii) Tetrahedron Letters, 2861 and 2865 (1968). 4. Chemistry of Natural products- Kalsi 5. Principles of organic synthesis by R. O. C. Norman and J.M.Coxon; Chapman and Hall 6. Classics in organic synthesis K. C. Nicolaou & E. J. Sorensen 7. J.Indian Inst.Sci. 81,287 (2001).

8. Medical Natural Products - A Biosynthetic approach by Paul M. Dewick 2 (Wiley) 9. Secondary metabolism - J. Mann, 2
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10. Chemical aspects of Biosynthesis J. Mann (1994). 11. i) J.C.S. Perkin Transactions II, 288-292, (1973). ii) J.Am.Chem.Soc. Vol.77.432-437, (1955).

CH 451 SYNTHETIC METHODS IN ORGANIC CHEMISTRY 1. Transition metal complexes in organic synthesis ; only Pd, Ni, Co, Pt, Fe, Rh, Ru; Grubbs catalyst, Ziegler Natta catalyst. 2. Use of Boron, Silicon and Tin in organic synthesis Ref.2, chapter 47 3. Designing of organic synthesis 4. Umpolung in organic synthesis. 5. Protection and deprotection of hydroxyl, amino, carboxyl, ketone and aldehyde functions as illustrated in the synthesis of polypeptide and polynucleotide. Solid phase peptide synthesis. (08) (20) (05) (15) (12) (60L)

Books/References: 1. Modern synthetic reactions H. O. House (Benjamin) 2. Organic chemistry J. Clayden, N. Greeves, S. Warren and P. Wothers (Oxford Press) 3. Designing of organic synthesis S. Warren (Wiley) 4. Some modern methods of organic synthesis W. Carruthers (Cambridge) 5. Organic synthesis M. B. Smith 6. Organometallics in organic synthesis J. M. Swan and D. C. Black (Chapman and Hall) 7. Advanced organic chemistry, Part B F. A Carey and R. J. Sundberg 5 edition (2007)
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CH 452 HETEROCYCLIC CHEMISTRY, CHIRON APPROACH & MEDICINAL CHEMISTRY Part A: Heterocyclic Chemistry 1. Five membered heterocycles Furan, Pyrrole and Thiophene (60L) (30L) (08)

2. Condensed five membered heterocycles Benzofuran, Indole and Benzothiophene. (05) 3. Pyridine, Quinoline and Isoquinoline 4. Rings with more than one heteroatom 1, 2 Azoles and 1, 3-Azoles, Purines and Pyrimidines. Ref. 1, 2, 3 Part B: Chiron Approach, Medicinal Chemistry etc. 1. Introduction of sugars, structures of triose, tetrose, pentose, hexose, stereochemistry and reactions of Glucose, conformation and anomeric effects in hexoses. Ref. 4, 5 2. Chiron Approach Ref. 6 (a) Introduction (b) Basic concepts carbohydrates, amino acids, hydroxy acids and terpenes. (c) The concept of chiral templates and chirons wherein the carbon skeleton is the chiral precursor. (d) Utilisation of the basic concepts for retrosynthetic strategy and synthesis of the following (S) Propanediol, (R) and (S) Epichlorohydrin, L (+)-Alanine, 11-Oxaprostaglandin F2, (-) Multistratin, (-) Pentenomycin, (-) Shikimic acid, Carbonolide B. 3. a) Green Chemistry Basic Principles including atom economy Ref. 7 b) Supramolecular chemistry. Ref. 8 c) Medicinal chemistry: introduction, physical-chemical properties and biologic activity, (02) (02) (12) (04) (30L) (10) (07)

theoretical aspects of drug design Ref.9

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Books: 1. Modern Heterocyclic chemistry L. A. Paquette (Benjamin). 2. Heterocyclic chemistry 3 edition Raj K. Bansal, New Age International (P) Ltd. (1999). 3. Heterocyclic chemistry J. A. Joule and K. Mills 4 edition Blackwell publishing (2007) 4. Organic Chemistry R. P. Morrison and R. N. Boyd 5. Organic Chemistry I. L. Finar, volume II 6. Chiron Approach in organic synthesis S. Hanessian 7. New Trends in Green Chemistry - V. K. Ahluwalia and M. Kidwai Anamaya Publishers (2004). 8. 9. Supramolecular Chemistry, vol.17 (1-2), pp.47-55, January-March 2005. Principles of Medicinal chemistry-W.O.Foye, Ed, 2nd Ed. Indian edition: K.M.Verghese Company
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PRACTICAL COURSES CH 347 TERNARY MIXTURE SEPARATION: Separation of at least ten mixtures containing three components. The mixtures should also involve separation of nitro phenols, amino acids, low boiling substances, water soluble substances. Amines, Phenols and acids used should also contain other elements and functional groups. The mixture separation should be carried out on micro-scale using ether.

CH 447 SINGLE STAGE AND TWO STAGE PREPARATIONS: At least eight single stage and eight two stage preparations from the following should be carried out. The preparations should be carried out on micro scale. Single Stage Preparations: 1. Acetophenone 2. Anthranilic acid Ethyl Benzene ortho Iodobenzoic acid

3. Diels-Alder reaction using Anthracene and Maleic anhydride 4. Benzyl cyanide 5. Bromobenzene 6. 2-Naphthol 7. Glycine 8. Salicylic acid 9. Resorcinol 10. 2-Methoxynephthalene 11. p-Xylene p-Nitro benzyl cyanide p-Nitro bromobenzene 2,2-Dihydroxybinaphthyl Hippuric acid 5-Nitrosalicylic acid Resacetophenone 1-Formyl-2-methoxynaphthalene Ter-phthalic acid
Base

12. o-Nitrotoluene + Benzaldehyde

condensation

Two Stage Preparations: 1. Benzophenone 2. Benzoin Benzil Oxime Benzanilide Benzilquinoxaline Benzalacetophenone Epoxide

3. Benzaldehyde + Acetophenone 4. 4-Nitrotoluene 5. Resorcinol

4-Nitrobenzoic acid 4-methyl-7-hydroxycoumarin

4-Aminobenzoic acid 4-methyl-7-acetoxy coumarin

6. Phenol 7. Cyclohexanone 8. 9. Acetanilide Hydroquinone

Salicyaldehyde Phenylhydrazone p-Nitroacetanilide Quinone Oxime Diacetate 4-Chlorophenyl acetate

Coumarin 1,2,3,4-tetrahydrocarbazole p-Nitroaniline 1,2,4- Triacetoxybenzene Caprolactum 2,5-Dihydroxy acetophenone 5-Chloro-2-hydroxyacetophenone

10. Cyclohexanone 11. Hydroquinone 12. 4-Chlorophenol

Interpretation of NMR, IR and Mass Spectra of about 15 compounds. Minimum 2 three stage preparations to demonstrate how to develop a synthetic sequence.

CH - 448 PROJECT AND PRACTICALS: 1. Students should carry out a small research project. This should make them familiar with literature survey, research methodologies, Identification of products by analytical and spectral methods and familiarity with chromatographic techniques. 2. Students who are not assigned the project should carry out at least 12 experiments and students who are assigned project work should carry out at least 6 experiments to illustrate the principles of organic reaction mechanism, stereochemistry or selectivity of reagents.

Suggested reagents and reactions LiAlH4 (reduction of ethyl benzoate to benzyl alcohol),NaBH4 ( reduction of anisaldehyde to p-methoxy benzyl alcohol), SeO2, NBS( bromination of p-nitrotoluene), Grignard Reaction( preparation of triphenyl carbinol or diphenyl methyl carbinol), Wittig Reaction (preparation of ethyl cinnamate from benzaldehyde), Cannizzaros reaction (on benzaldehyde) Asymmetric reduction, Phase transfer catalyst isolation of natural products (like Eugenol from cloves, Limonene from orange peels, Trimyristin from nutmeg etc.), photochemical reaction, Peracid and lead tetra acetate oxidation, rearrangement reactions, synthesis of heterocyclic compounds like Hydantoin, thiohydantoin, pyrazolone, Biginelli reaction (synthesis of 4-aryl-3,4-dihydropyrimidinone) Important Notes: 1. All theory and practical courses are university courses. 2. Each theory course is of 60 lectures. 3. Practicals should be carried out on micro scale. 4. Each practical course should be given six hours of laboratory work per week and the course will be extended over two semesters and will be examined at the end of the year. 5. Practical batch will consist of not more than 10 students. 6. At least 25 % students should be assigned the projects. 7. The weightage to the project will be of 50 marks and will be examined by the oral examination and presentation. There will be a single stage preparation of 30 marks along with project. 8. Students who are not assigned the project work have to carry out one two-stage preparation and two single stage preparations from the suggested reagents and reactions for 60 marks and undergo oral examination for 20 marks. 9. Post graduate departments should arrange at least one industrial visit. 10. All required chemicals must be made available for practicals and certified journals should be shown to the examiner.