SYLLABUS FOR MASTER OF SCIENCE ORGANIC CHEMISTRY PART- II. (Semester III and IV)

Transcription

1 NORTH MAHARASHTRA UNIVERSITY, JALGAON SYLLABUS FOR MASTER OF SCIENCE In ORGANIC CHEMISTRY PART- II (Semester III and IV) w. e. f. June 2015

2 NORTH MAHARASHTRA UNIVERSITY, JALGAON Syllabus for M.Sc. Part-II Organic Chemistry (Semester - III & IV) (With Effect from June 2015) Course Structure for Second Year The following will be the structure for revised syllabus from June 2015 for semester III and semester IV SEMESTER - III Sub. Code: Title CH-350: Organic Reaction Mechanism CH-351: Spectroscopic Methods in Structure Determination CH-352: Organic Stereochemistry CH-353: Free radical, photochemistry, pericyclic reaction and their applications SEMESTER - IV Sub. Code: Title CH-450: Chemistry of Natural Products CH-451: Synthetic Methods in Organic Chemistry CH-452: Heterocyclic chemistry, chiron approach, chiral drugs and medicinal chemistry Practical courses: Sub. Code: Title CH -O-2: Ternary mixture separation (Annual) CH -O-3: Three stage preparations (Annual) CH -O-4: Short Research Project (Annual)

3 Important Notes 1. Each theory course prescribed for M. Sc. should be covered in 4 lectures, each of 60 minutes duration per week per course including lectures, tutorials, seminars etc. (Total 60 hrs / theory course) 2. Each practical course will require 6 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. (Total 180 hrs / practical course) 3. There should not be more than 10 students in a batch for M. Sc. Practical course. 4. For theory course the question paper should include at least 20 % weightage for problem solving. Problem solving would include numerical, short answer, long answer questions to test understanding of the subject. 5. Of the 60 lectures in each course about 10 lectures will include tutorials, student seminars, classroom discussions and tests. 6. The marks for each paper are distributed as external examination 80 marks and internal examination 20 marks. For internal assessment of each theory and practical course, 2 written tests will be taken in which best will be considered for internal marks. 7. Students should visit at least two chemical industries in two years of M. Sc. and submit the observations/report to the Department.

4 SEMESTER-III CH-350: ORGANIC REACTION MECHANISM (60L) 1. Physical Organic Chemistry (15L) Hammett plot, Hammett equation, substituent and reaction constants, physical significance of substituent and reaction constants, substituent constant involving through conjugation. Use of Hammett plot and equation. Deviations from straight line plot. Concave upward deviation. Concave downward deviation. Steric effects, Taft equation, Steric parameters, solvent effect, change of reaction constant. 2. Carbanions-Formation, stability and related name reactions (15L) Aldol Condensation, Bezoin Condensation, Michael Addition, Mannich reaction, Reimer-Tiemann reaction, Knoevengal reaction, Dieckmann reaction, Perkin reaction, Stobbe reaction, Halogenation of Ketone(Acid & Base catalysed), Darzen Condensation reaction, Claisen Ester condensation. Enamines-: Formation and Applications 3. A) Neighbouring group participation (7L) Mechanism and effects of anchimeric assistance, NGP by unshared/ lone pair electrons, π-electrons, aromatic rings, σ-bonds with special reference to bornyl and norbornyl systems (formation of nonclassical carbocation) B) Reactive Intermediate (8L) Organic reactive intermediates, methods of generation, structure, stability and important reactions involving carbocations, nitrenes, carbenes, arynes and ketenes. 4. Ester Hydrolysis (Acid & Base catalysed) (15L) A 1 Ac, A Ac 2, B Ac 2, B AL 1, B AL 2, A AL 1 Decaboxylation References:- 1. A guide book to mechanism in Organic Chemistry 6 th edition, By Peter Sykes: Orient Longman 2. Mechnism and structure in Organic Chemistry, Edwin S. Gould, Holt, Rinechart and Winston. 3. Organic Chemistry 5 th edition, By S. H. Pine. MaGraw-Hill International editions.

5 4. Advanced Organic Chemistry 3 rd edition, by R. O. C. Norman and J. M. Coxon 3 rd edition ELBS. 5. Advanced Organic Chemistry Part A and B 2 nd edition, by F. A. Carey and R. J. Sundberg. Plenum Press. New York and London. 6. Organic Chemistry-Clayden, Greeves, Warren and Wothers, OXFORD. 7.Advanced organic chemistry by J.March 6 th Edition 8.Organic Reaction Mechanism by P.S.Kalsi 9.Organic reaction & Mechanism by Sanyal CH-351: Spectroscopic Methods in Structure Determination 1. Proton Magnetic Resonance: (12 L) Recapitulation, advanced ideas of chemical shift, chemical exchange, effect of deuteration, stereochemistry, hindered rotation, identification of complex spin system. AB, ABC, ABX and AMX systems. Factors affecting vicinal and germinal coupling, long range coupling. Simplification of complex spectra, nuclear double resonance, nuclear overhauser effect, shift reagents. 2. Two Dimensional NMR Correlation Spectroscopy: (12L) Two dimensional NMR spectroscopy, 2D-HETCOR, 1H-1H COSY, types of COSY experiments, 2D TOCSY, NOSEY, ROSEY, J resolved 2D NMR spectroscopy, HSQC, HMQC and HMBC C NMR spectroscopy (12L) 13 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) 4. Mass Spectroscopy: (12L) Instrumentation, various methods of ionization (field ionization, field desorption, 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: (12L) Based on joint application of U.V., I.R., NMR, CMR and Mass spectroscopy (including reaction sequence and spectral analysis).

6 References: 1. Introduction to Spectroscopy D. L. Pavia, G.M. Lampman, G. S. Kriz, 3rd Ed. (Harcourt college publishers). 2. Spectrometric identification of organic compounds R. M. Silverstein, F. X. Webster, 6th 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) 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. 4th Ed. John Wiley and sons Ltd Spectroscopic identification of organic compound- R M Silverstein, G C Bassler and T C Morril, John Wiley 11. Introduction to NMR spectroscopy-r J Abrahm, J Fisher and P loftus Wiley 12. Organic spectroscopy-william kemp, E L B with McMillan 13. Spectroscopy of organic molecule-ps Kalsi,Wiley, Esterna, New Delhi 14. Organic spectroscopy-rt Morrison and RN Boyd 15. Practical NMR spectroscopy-ml Martin, J J Delpench, and D J Martyin 16. Spectroscopic methods in organic chemistry-d H Willson, I Fleming 17. Spectroscopy in organic chemistry- C N R Rao and J R Ferraro 18. NMR Basic principle and application-h Guntur 19. Interpretation of NMR spectra-roy H Bible 20. Mass spectrometry organic chemical applications, J H Banyon

7 CH-352: Organic Stereochemistry 1. Principles of stereochemistry: (12 L) Configurational and conformational isomerism in acyclic and cyclic compounds; stereogenicity, stereoselectivity, enantioselectivity, diastereoselectivity and asymmetric induction. 2. Asymmetric synthesis: (12 L) Chiral auxiliaries, methods of asymmetric induction substrate, reagent and catalyst controlled reactions; determination of enantiomeric and diastereomeric excess; enantio-discrimination. Resolution - optical and kinetic. Racemic modification and resolution of racemic mixture. 3. Stereochemistry of 6-membered ring & their reactions: (12 L) Shape of cyclohexane ring, disubstituted cyclohexane-1,2 & 1,3 & 1,4 disubstituted cyclohexanes, physical properties (energy calculation), conformational effects in six member ring containing unsaturation, six member heterocyclic ring. 4. A) Stereochemistry of ring other than six membered five membered, rings larger than six (06 L) membered medium rings, conformational effects in medium rings, trans annular effects concepts of I- strain. B) ORD & CD : (06L) Nomenclature, Principal, application to structure, octant & axial haloketones rule. 5. Fused ring and Bridge rings Bicyclic & polycyclic, occurrence, availability stereochemical (12L) reactions & reactions of norboryl system. References: 1. Stereochemistry of carbon compounds. E L. Eliel. 2. Conservation of Orbital symmetry. R. B. Woodward and Hofmann. 3. Stereochemistry. D. Nasipuri. 4. Orbital Symmetry: Problem Solving Approach. R. E. Lehr and Merchand. 5. Frontial orbitals and Organic Chemical Reactions. I N Flaming.

8 6. Organic Chemistry- by Finar 7. Organic Chemistry-Clayden, Greeves, Warren and Wothers----OXFORD 8. Stereoselective synthesis Mihaly Nograd VCH, Weinheim, Principles and applications of Asymmetric Synthesis Gou-Qiang Lin, Yue-Ming Li and S. C. Chan---Wiley-Interscience, John Wiley and Sons, Inc. Publication CH-353: Free radical, photochemistry, pericyclic reaction and their applications 1. Free Radicals (20 L) Formation,Stability & Detection of long & Short-Lived radicals,homolysis & Free radical displacement(substitution),addition and Rearrangement reactions of free radicals,radical Cyclonization in Synthesis,other types of free radical reaction(halogen,sulphur,and, Selenium Group transfer reaction) 2. Photochemistry (20 L) 2.1 Principles of photochemistry: quantum yield, electronic states and transitions, selection rules, modes of dissipation of energy (Jablonski diagram), electronic energy transfer: photosensitization and quenching process. 2.2 Photochemistry of carbonyl compounds: π π*, n π* transitions, Norrish-I and Norrish-II cleavages, Paterno-Buchi reaction. Photoreduction, calculation of quantum yield, photochemistry of enones, photochemical rearrangements of α, β-unsaturated ketones and cyclohexadienones. Photo Fries rearrangement, Barton reaction. 2.3 Photochemistry of olefins: cis-trans isomerizations, dimerizations, hydrogen abstraction, addition and Di- π- methane rearrangement including aza-di- π -methane. 2.4 Photochemistry of arenes: 1, 2-, 1, 3- and 1, 4- additions. 2.5 Singlet oxygen and photooxygenation reactions. 3. Pericyclic Reaction (20L)

9 Pericyclic reactions: Classification of pericyclic reactions; thermal and photochemical reactions. Three approaches: Conservation of orbital symmetry - Correlation diagram, Frontier molecular orbital approach [FMO] and Aromatic transition state approach [Huckel and Mobius]. Cycloaddition reactions: 4nπ and (4n+2)π electron systems. Diels-Alder reactions,1, 3-Dipolar cycloaddition and cheletropic reactions, ene reaction, retro-diels-alder reaction,regioselectivity, periselectivity, site selectivity and effect of substituents in Diels-Alder reactions. 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, 5th 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). 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, 2nd Ed. T. L. Gilchrist and R. C. Storr; Cambridge 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, (1981) SEMESTER-IV CH-450: Chemistry of Natural Products 1. Structure, Stereochemistry and Biogenesis of Hardwickiic acid, Camptothecin and Podophyllotoxin. (10L) 2. Synthesis of Some Natural Products (18 L) i) Reserpine (Woodward synthesis) ii) Taxol iii) Estrone and Mifepristone iv) Strychnine (Overman s synthesis) v) Fredericamycin A

10 3. Chemistry of Natural Products such as Carbohydrates, proteins and peptides, fatty acids, nucleic acids and Lipids. (12L) 4. Vitamins (12L) Classification, sources and biological importance of vitamin B1, B2, B6, folic acid, B12, C, D1, E (α-tocopherol), K1, K2, H (β- biotin). Synthesis of the following: Vitamin B1 including synthesis of pyrimidine and thiazole moieties Vitamin B2 from 3, 4-dimethylaniline and D(-)ribose Vitamin B6 from: 1) ethoxyacetylacetone and cyanoacetamide 2) ethyl ester of N-formyl-DL-alanine( Harris synthesis) Vitamin E (α-tocopherol) from trimethylquinol and phytyl bromide Vitamin K1 from 2-methyl-1, 4-naphthaquinone and phytol. 5. Enzymes (08L) Chemistry of enzymes: Introduction, nomenclature, classes and general types of reactions catalyzed by enzymes. Properties of enzymes: i) Enzyme efficiency/catalytic power ii) Enzyme specificity; Fischer s lock and key and Koshland induced fit hypothesis. Concept and identification of active site. Factors affecting enzyme kinetics: Substrate concentration, enzyme concentration, temperature, ph, product concentration etc. Reversible and irreversible inhibition. References: 1 Enzyme catalysis in organic synthesis, 3rd edition. Edited by Karlheinz Drauz, Harold Groger, and Oliver May, Wiley-VCH Verlag GmbH & Co KgaA, Biochemistry, Dr U Satyanarayan and Dr U Chakrapani, Books and Allied (P) Ltd. 3. Bioorganic, Bioinorganic and Supramolecular chemistry, P.S. Kalsi and J.P. Kalsi. New Age International Publishers 4. The Organic Chemistry of Enzyme-Catalysed Reactions, Academic Press, By Richard B. Silverman 5. Enzymes: Practical Introduction to structure, mechanism and data analysis, By Robert A. Copeland, Wiley-VCH, Inc. 6. The Organic Chemistry of Biological Pathways By John McMurry, Tadhg Begley by Robert and company publishers 7. Biochemistry By Lehninger

11 CH-451: Synthetic Methods in Organic Chemistry 1. Transition metal complexes in organic synthesis ; only Pd, Ni, Co, Pt, Fe, Rh, Ru, Grubb s catalyst, Ziegler Natta catalyst. (12) 2. Designing of organic synthesis (20) 3. Umpolung in organic synthesis. Nitrogen, Phosphorous and Sulphur Ylides in Organic Synthesis. (08) 4. Protection and deprotection of hydroxyl, amino, carboxyl, ketone and aldehyde functions as illustrated in the synthesis of polypeptide and polynucleotide. (08) Solid phase peptide synthesis. 5. Green Chemistry (12L) Introduction, basic principles of green chemistry. Designing a green synthesis: Green starting materials, green reagents, green solvents and reaction conditions, green catalysts. Use of the following in green synthesis with suitable examples: a) Green reagents: dimethylcarbonate, polymer supported reagents. b) Green catalysts: Acid catalysts, oxidation catalysts, basic catalysts, phase transfer catalysts [Aliquat 336, benzyltrimethyl ammonium chloride (TMBA), Tetra-n-butyl ammonium chloride, crown ethers], biocatalysts. c) Green solvents: water, ionic liquids. d) Solid state reactions: solid phase synthesis, solid supported synthesis. e) Microwave assisted synthesis: reactions in water, reactions in organic solvents, solvent free reactions. f) Ultrasound assisted reactions. Comparison of traditional processes versus green processes in the syntheses of ibuprofen, adipic acid, 4-aminodiphenylamine, p-bromotoluene and benzimidazole. 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)

12 7.Green Chemistry: An Introductory Text, 2nd Edition, Published by Royal Society of Chemistry, Authored by Mike Lancater 8. Organic synthesis in water. By Paul A. Grieco, Blackie. 9. Green chemistry, Theory and Practical, Paul T.Anastas and John C.Warner. 10. New trends in green chemistry By V.K.Ahulwalia and M.Kidwai, 2nd edition, Anamaya Publishers, New Delhi 11. An introduction to green chemistry, V.Kumar, Vishal Publishing Co CH-452:Heterocyclic Chemistry, Chiron Approach, Chiral Drugs and Medicinal Chemistry (60L) 1. Heterocyclic Chemistry- Synthesis and Reactions (30 L) i. Five Member Heterocycles- Furon, Pyrrol and Thiophine. (08 L) ii. Condensed five member heterocycles- Benzofuran, Indol, Benzothiophine. iii. Pyrridine, Quinoline and Isoquinoline. (05L) (07L) iv. Ring more than one heteroatom- 1,2 Azoles, 1,3 Azoles, Purines and Pyrimidines. (10L) 2. Chiron Approach, Chiral Drugs and Medicinal Chemistry 30L i. Carbohydrates Introduction of Sugar, Structure of triose, Pentose, hexose, Stereochemistry and reaction of Glucose, Confirmation and anomeric effects in hexoses ii. Chiron approach: Introduction Basic concepts Carbohydrates, amino acid, hydroxyl acids and terpenes. The concept of chiral templates and Chirones where in the carbon skeleton is the chiral precursor. Utilization of the basic concepts for retro synthetic strategy and synthesis of-(s) Propane diol,(r) and (S) epichlorohydrin, L(+) alanine, 11-oxyaprotogladine F-2a, (-) Multistrain (-) pentanomycin. iii. Chiral Drugs: Introduction to chiral drugs, eutomers, distomer and eudesmic ratio. Synthesis and Pharmacological activity of S-Ibuprofin, S-Metaprolol, (+) Ephedrime. iv. Medicinal Chemistry:

13 Introduction, Important Terms used in medicinal chemistry- Receptor therapeutic index, Bioavailability, Drug assay and Drug Potency. General idea of factor affecting bioactivity- Resonance, inductive effect, bioisosterism, spatial considerations. Basic Pharmacokinetics Drug Absorption, Distribution, Metabolism(Biotransformation) and elimination. Physical and Chemical Parameters like solubility, lipophilicity, Ionisation, PH,Redox potential,hydrogen bonding, Partition coefficient and isomerism in drug distribution and drug receptor binding. Introduction to anti Microbial drugs-antifungal, Antibacterial, antiviral, antiprotozoals. Reference: 1. Modern Heterocyclic Chemistry- L.A. Paquette 2. Heterocyclic Chemistry 3 rd Ed.- Raj Bansal (New age Publi.) 3. Heterocyclic Chemistry 4 th Ed.- J.A. Joules and K. Mills (Blackwell Publi.) 4. Organic Chemistry R.P. Morrison and R.N. Boyd (LPE) 5. Organic Chemistry-I.L.Finar Vol-II 6. Chiron Approach in Organic Synthesis- S. Hanessain 7. Pharmaceutical Chemistry and Drug Synthesis- Rot and Kleeman. 8. Drug Design E.J. Arienes 9. Medicinal Chemistry- Foye 10. Medicinal Chemistry- Ashutosh Karr 11.Medicinal Chemistry G R. Chatwal. Semester IV: Practicals Course Code: CH-O-2 Separation of solid-liquid/ liquid-liquid ternary mixture using micro-scale technique 1. Separation of components of ternary mixtures (solid-liquid or liquid-liquid) based upon differences in the physical and the chemical properties of the components. 2. Purification of the three components, and determination of their physical constants. 3. Calculation of percentage yield of the individual components. (Minimum 6 experiments)

14 Course Code: CH-O-3 Three stage preparations (Starting with 5g or less.)monitored by TLC 1. Preparation of Benzanilide by Beckmann rearrangement. 2. Preparation of Anthranilic acid. 3. Preparation of Phthalimde. 4. Preparation of p-aminobenzoic acid. 5. Preparation of N-Bromosuccinamide. 6. Preparation of p-chloronitrobenzene by Sandmeyer reaction. 7. Preparation of p-iodonitrobenzene by Sandmeyer reaction. 8. Pinocol-pinacolone rearrangement. 9. Preparation of Acetophenone by Fries rearrangement. 10. Preparation of aromatic aldehydes by Vilsmeier-Hack reaction or Reimer-Tiemann. 11.Wittig reaction. CH -O-4: Short Research Project Literature survey, studies of reactions, synthesis, mechanism, isolation of natural products, standardization of reaction conditions, new methods etc.