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Molecular Rearrangements and Reactive Intermediates in Organic Synthesis

By Prof. Santanu Panda   |   IIT Kharagpur
Learners enrolled: 843   |  Exam registration: 118
ABOUT THE COURSE:
Molecular rearrangements in organic synthesis involve the transformation of the structure of a molecule by the movement of atoms or groups of atoms within the molecule. These rearrangements play a crucial role in the synthesis of organic compounds, allowing chemists to create complex structures from simpler starting materials. Molecular rearrangements can be classified into various types, and they are often named based on the specific changes occurring in the molecule such as 1,2-metallate rearrangement, Cope Rearrangement, Claisen Rearrangement, Wagner-Meerwein Rearrangement, Pinacol Rearrangement, Beckmann Rearrangement, Fries Rearrangement, Baeyer-Villiger Oxidation and so on. This is aprivileged tool towards chemists and biochemists providing access to control the structure-reactivity relationship.

INTENDED AUDIENCE: Students of BSMS/BSc/MS/MSc and PhD can benefit from this course.

PREREQUISITES: Basic Concept of Organic Chemistry

INDUSTRY SUPPORT: Syngenta Goa, PI Industries Jaipur, TCG life science Kolkata, Merck India Pvt. Ltd. Zoetis India Pvt. Ltd and other chemical industry across India and around the world
Summary
Course Status : Completed
Course Type : Core
Language for course content : English
Duration : 12 weeks
Category :
  • Chemistry
Credit Points : 3
Level : Postgraduate
Start Date : 22 Jul 2024
End Date : 11 Oct 2024
Enrollment Ends : 05 Aug 2024
Exam Registration Ends : 16 Aug 2024
Exam Date : 26 Oct 2024 IST

Note: This exam date is subject to change based on seat availability. You can check final exam date on your hall ticket.


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Course layout

Week 1: Introduction to reactive intermediates such as carbocation, carbanion, carbene, nitrene, and free radicals;
Carbocation:  stability of carbocations, classification, and their stability comparison, carbocation generation, various carbocationic rearrangements including Wagner-Meerwein Rearrangement, Pinacol-pinacolone rearrangement, Beckman rearrangement, 

Week 2: Carbanion: Structure, stability, and Molecular rearrangements using carbanions as the reactive intermediate. Claisen Rearrangement: -Ireland-Claisen, Johnson-Claisen, Eschenmoser-claisen, Overmann- Claisen with mechanism, example and application [2,3] Wittig rearrangement, [1,2] Wittig rearrangement, Stevens rearrangement, Sommelet–Hauser rearrangement, Benzilic acid rearrangement, Favorskii Rearrangement, Neber Rearrangement, Smiles rearrangement, Payne Rearrangement, Baker–Venkataraman rearrangement, Ramberg-Bäcklund Reaction etc.

Week 3: Carbene: history, definition, characteristic, different types of carbene, molecular orbital diagram of different carbene, singlet carbene, triplet carbene, persistent carbene, metallocarbene, various methods for
generation of carbene: via fragmentation reaction-1) from diazo compounds, 2) from tosylhydrazone, 3) from ketene, 4) from the three-membered strained ring, 5) from strained alkene; via α-elimination, various reactions of carbene: addition reaction, insertion reaction, cyclopropanation, Name reactions: Simmons-Smith reaction, Bamford-Steven’s reaction, Shapiro reaction, Wolff rearrangement, alkene metathesis.

Week 4: Nitrene: Structure, stability, synthesis, and the transformations using Nitrenes. Curtius Rearrangement, Lossen Rearrangement, Schmidt Reaction, etc.

Week 5: Radicals: Definition, history, various radical formation methods: abstraction, addition, elimination. radical analyzation method: ESR, radicals stability and reactivity, various reactions of radical: HBr addition, chlorination, fluorination and iodination of alkanes/alkenes, radical chain reactions. Regiochemistry of HBr addition, carbon-carbon bond formation using radicals, nucleophilic vs electrophilic radicals, intramolecular vs intermolecular radical reactions, radical polymerization, and application of free radicals.

Week 6: Molecular rearrangements using free radicals. Different examples of molecular rearrangement using free radicals. 
Different photoreactions using free radical; Barton Nitrite Photolysis Reaction, Barton Decarboxylation, Barton-McCombie Deoxygenation, Hunsdiecker Reaction, Birch Reduction, Chain Walking in Polymerization, Norrish Type I and Type II , Electron transfer reaction: Kolbe electrolysis, radical coupling reactions, aromatic substitution reaction using free radical; Sandmeyer reaction

Week 7: Benzyne: Structural features, comparison study with acetylene and benzene, methods of benzyne generation: Deprotonation of aryl halide using strong base, metal halogen exchange and elimination, from anthranilic acid, fragmentation, Kobayashi and Hosoya methods of aryne generation, activation by cesium carbonate, Different types of reaction using benzyne intermediate like pericyclic reaction, arylation reaction, insertion reaction, metal-catalyzed reaction, molecular rearrangements and multicomponent reaction.

Week 8: Reactive intermediates of Si-based reagents towards organic synthesis: The nature of silicon bonding, Comparison between carbon and silicon, Alpha and beta effect of silicon, Nucleophilic substitution at silicon, Silicon-based protection of alcohol, TMS-OTf, TMS-CN, Alkynyl silanes in protection and activation, Ipso substitution of aryl silanes, Reactivity of vinylsilanes, Allyl silanes as nucleophiles, hydrosilylation, Hiyama coupling, The Peterson elimination, Brook rearrangement. Silyl-Heck coupling, Silyl-Negishi coupling.

Week 9: Reactive intermediates of P-/S- towards the organic synthesis. 
Sulfur:
Sulfur ylide chemistry, Sulfur-stabilized anions, Julia Olefination, Addition Reactions with Electrophilic Sulfur and Selenium Reagents, Rearrangement of Allylic Sulfoxides, Pummerer rearrangement, Swern oxidation, Bamford-Stevens reaction, Barton radical decarboxylation reaction, Chugaev elimination reaction, Corey-Chaykovsky epoxidation and cyclopropanation, Corey-Kim oxidation, Kornblum oxidation, Mislow-Evans rearrangement, Ramberg-Bäcklund rearrangement, Smith-Tietze multicomponent dithiane linchpin coupling.
Phosphorous:
Appel reaction, Mitsunobu reaction, Arbuzov reaction, Wittig reaction, Horner–Wadsworth–Emmons reaction, E vs Z olefin, aza-Wittig reaction, Corey-Fuchs alkyne synthesis, Corey-Nicolaou macrolactonization, Corey-Winter olefination, Seyferth-Gilbert homologation, Staudinger reaction, Vilsmeier-Haack formylation.

Week 10: Organoboron: Reactive intermediates using boron and some basic transformations. Hydroboration, oxidation, Cross-coupling reaction, radical transformations. Molecular rearrangements using organoborons. 1,2-metallate rearrangement, Matteson homologation, Aggarwal homologation, Zweifel olefination, Boron-Wittig reaction.

Week 11 & 12: Various organometallic reagents such as organolithium: basic concepts, reactivity, basicity, nucleophilicity characters, chelation property, structures in various solvent, reactivity in different solvent, M.O- diagram, generation, deprotonation, transmetallation, metal-halogen exchange, various reactions, direct lithiation, formation of aldehyde, ortho-lithiation, umpulong effect, asymmetric synthesis; Grignard: definition, mechanism, structure, different types of Grignard reagent, synthesis; organozinc: synthesis, structure, reactivity, synthetic method, activated Zn- powder, Rieke- Zn, transmetallation, halogen Zn- exchange, different reaction, the reactivity of diethyl zinc, Negishi coupling, Reformatsky reaction, Blaise reaction, Simon-smith reactions; Organo Copper reagent: Gilmann’s reagent, synthesis, example, comparison with Grignard reagent.

Books and references

1. Organic Chemistry 2nd Edition, by J. Clayden, S. Warren, N. Greeves, P. Worthers, Oxford University Press, ISBN-13 978-0199270293.
2. Advanced Organic Chemistry (Part B: Reactions and synthesis) by F. A. Carey and R. J. Sundberg, 5th Corrected ed, 2008, ISBN-13: 978-0387683546.
3. Modern Methods of Organic Synthesis by William Carruthers and Ian Coldham, CambridgeUniversity Press; 4th edition, 2004, ISBN-13: 978-0521778305.
4. Heterocyclic Chemistry, 5th Edition, 2010, by John A. Joule, Keith Mills, ISBN: 978-1-405-13300-5.
5. Strategic Applications of Named Reactions in Organic Synthesis, by Barbara Czako and Laszlo Kurti, Academic Press; 1st edition 2005, ISBN-13: 978-0124297852.
6. Organic Chemistry Vol 1 by I. L. Finar, Pearson Education India; 6th edition, 2002, ISBN-13 : 978-8177585421.
7. March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley- Blackwell; 6th edition, ISBN-13: 978 0471720911.
8. Molecular Orbitals and Organic Chemical Reactions, Wiley; 1st edition 2011, by Ian Fleming,ISBN: 978-0470-74658-5.

Instructor bio

Prof. Santanu Panda

IIT Kharagpur
Prof. Santanu Panda received his PhD in Chemistry from Case Western Reserve University, USA, under the supervision of Prof. Anthony Pearson in the research area of asymmetric catalysis and total synthesis of natural products. He continued his scientific education as a Postdoctoral Fellow under Prof. Joseph Ready at UT Southwestern Medical Center, USA in the field of organ boron chemistry and developed methods to access substituted pyridines and optically active indoles. He joined the Department of Chemistry, Indian Institute of Technology Kharagpur in July 2018 as an assistant professor. He has taught a variety of UG and PG courses at IIT Kharagpur and received several recognitions including the Ramanujan fellowship from SERB, the Merck Young Scientist award from Merck India Pvt. Ltd, Bronze medal from CRS, and more. His research group is focusing on the development of synthetic methodologies and their application to the synthesis of important drugs and bioactive compounds.

Course certificate

The course is free to enroll and learn from. But if you want a certificate, you have to register and write the proctored exam conducted by us in person at any of the designated exam centres.
The exam is optional for a fee of Rs 1000/- (Rupees one thousand only).
Date and Time of Exams: 
26 October 2024 Morning session 9am to 12 noon; Afternoon Session 2pm to 5pm.
Registration url: Announcements will be made when the registration form is open for registrations.
The online registration form has to be filled and the certification exam fee needs to be paid. More details will be made available when the exam registration form is published. If there are any changes, it will be mentioned then.
Please check the form for more details on the cities where the exams will be held, the conditions you agree to when you fill the form etc.

CRITERIA TO GET A CERTIFICATE

Average assignment score = 25% of average of best 8 assignments out of the total 12 assignments given in the course.
Exam score = 75% of the proctored certification exam score out of 100

Final score = Average assignment score + Exam score

YOU WILL BE ELIGIBLE FOR A CERTIFICATE ONLY IF AVERAGE ASSIGNMENT SCORE >=10/25 AND EXAM SCORE >= 30/75. If one of the 2 criteria is not met, you will not get the certificate even if the Final score >= 40/100.

Certificate will have your name, photograph and the score in the final exam with the breakup.It will have the logos of NPTEL and IIT Kharagpur .It will be e-verifiable at nptel.ac.in/noc.

Only the e-certificate will be made available. Hard copies will not be dispatched.

Once again, thanks for your interest in our online courses and certification. Happy learning.

- NPTEL team


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