Lecture-1 Department of Chemistry INTRODUCTION
Aromaticity and Stereochemistry
Dr. L. Satish K. Achary Assistant Professor Syllabus for Organic Chemistry Unit- I: Aromaticity and Stereochemistry Aromaticity and anti-aromaticity, Hückel’s rule, anti-aromaticity, y-aromaticity, homo-aromaticity, Cyclodextrins, catenanes and rotaxanes.
Stereochemistry: Conformational analysis of cycloalkanes, effect of conformation on reactivity. Elements of symmetry, Chirality of organic molecules with or without chiral centres, molecules with more than one chiral center, projection formulae (i) Fischer (ii) Sawhorse (iii) Newman (iv) Flying Wedge; Homotopic, enantiotopic and diastereotopic atoms, groups and faces. Stereospecific and stereoselective synthesis. Asymmetric synthesis. Optical activity in the absence of chiral carbon.
Unit- II: Structure and Reactivity Structure and Reactivity: Types of mechanisms, types of reactions, thermodynamic and kinetic requirements, Hammond postulate, Curtin-Hammett principle, transition states and intermediates, methods of determining mechanisms, isotopic effects. Generation, structure, stability and reactivity of carbocations, carbanions, free radicals, carbenes and nitrenes. Effect of structure on reactivity. The Hammett equation and linear free energy relationship (sigmarho) relationship, Taft equation. 16-12-2020 2 www.youtube.com/c/powerupwithpowerpoint Unit-III: Aliphatic Nucleophilic and Electrophilic Substitution Aliphatic Nucleophilic Substitution: The SN2, SN1, mixed SN1 and SN2 and SET mechanisms. Reactivity effects of substrate structure, attaching nucleophile, leaving group and reaction medium. The neighbouring group mechanism. The SNi mechanism. Nucleophilic substitution at an allylic, aliphatic trigonal and a vinyl carbon. Aromatic Nucleophile Substitution: The SNAr, SN1, benzyne and SRN1 mechanisms. Reactivity; effect of substrate structure, leaving group and attacking nucleophile. Aliphatic Electrophilic Substitution: Bimolecular mechanisms: SE1, SE2 and SEi. The SE1 mechanism, electrophilic substitution accompanied by double bond shifts. Effect of substrates, leaving group and the solvent polarity on the reactivity. Aromatic: The arenium ion mechanism, orientation and reactivity, energy profile diagrams. The ortho/para ratio, ipso attack, orientation in other ring systems. Quantitative treatment of reactivity in substrates and electrophiles.
Unit-IV: Addition reactions Addition to Carbon-Carbon Multiple Bonds: Mechanistic and stereochemical aspects of addition reactions involving electrophiles, nucleophiles and free radicals, regio- and chemo-selectivity, orientation and reactivity. Addition to cyclopropane ring. Hydroboration. Addition to Carbon-Hetero Multiple Bonds: Mechanism of metal hydride reduction of saturated and unsaturated carbonyl compounds, acids, esters and nitriles. Addition of Grignard reagents, organozinc and organolithium reagents to carbonyl and unsaturated carbonyl compounds. 16-12-2020 3 www.youtube.com/c/powerupwithpowerpoint Unit-V: Free Radical and Elimination Reactions Free Radical Reactions: Types of free radical reactions, free radical substitution mechanism, mechanism at an aromatic substrate, neighbouring group assistance. Reactivity for aliphatic and aromatic substrates at a bridgehead. Reactivity in the attaching radicals. The effect of solvents on reactivity.
Elimination Reactions: The E2, E1 and E1cB mechanisms and their spectrum. Orientation of the double bond. Reactivity; effects of substrate structures, attaching base, the leaving group and the medium.
16-12-2020 4 www.youtube.com/c/powerupwithpowerpoint Books Jagdamba Singh and L.D.S Yadav Advanced Organic Chemistry, Pragati prakashan. G. S. Zweifel and M. H. Nantz. “Modern Organic Synthesis-An Introduction”,W. H. Freeman and Company, 2006. March’s Advanced Organic Chemistry Reactions, Mechanisms, And Structure Wiley-interscience A John Wiley & Sons, Inc., Publication. Trost B. M. and Fleming I. Comprehensive Organic Synthesis, Pergamon Press.
16-12-2020 5 www.youtube.com/c/powerupwithpowerpoint Aromaticity
16-12-2020 3 C. V. Raman Global University, Odisha Contents
01 Introduction
02 Aromatic antiaromatic and non-aromatic
03 Huckel's rule
04 Annulene
06 Some examples
16-12-2020 1 C. V. Raman Global University, Odisha Introduction Aromaticity
Aromatic Non-aromatic Antiaromatic
16-12-2020 2 C. V. Raman Global University, Odisha Conditions Cyclic and Planar
Conjugated π system
sp2 or sp hybridized ring carbon
Ring atom with unhybridized p-orbital in continuous overlapping.
Huckel’s rule
Energy and stability
16-12-2020 2 C. V. Raman Global University, Odisha Cyclic and Planar
16-12-2020 10 C. V. Raman Global University, Odisha Conjugated π system
16-12-2020 11 C. V. Raman Global University, Odisha sp2 or sp hybridized ring carbon
16-12-2020 12 C. V. Raman Global University, Odisha Ring atom with unhybridized p-orbital in continuous overlapping
16-12-2020 13 C. V. Raman Global University, Odisha Huckel’s rule If the compound is cyclic, planar, fully conjugated & posses (4n +2) π electrons, then it is an aromatic compound.
If the compound is cyclic, planar, fully conjugated & posses 4n π electrons, then it is an anti-aromatic compound. where n is any integer like 1,2,3,……..
16-12-2020 14 C. V. Raman Global University, Odisha Aromatic Antiaromatic Non-aromatic
Cyclic and Planar Cyclic and Planar Cyclic/Acyclic
Conjugated π system Conjugated π system Planar/Non-planar
sp2 or sp hybridized sp2 or sp hybridized May follow 4n+2 or 4n ring carbon ring carbon rule
Ring atom with Ring atom with Conjugate/Non-conjugate. unhybridized p-orbital in unhybridized p-orbital in continuous overlapping. continuous overlapping.
4n+2 π system 4n π system More energy than aromatic and less than Low energy and high High energy and low antiaromatic stability stability 16-12-2020 4 C. V. Raman Global University, Odisha N.A A.A A
A.A A A
N.A A.A A
16-12-2020 N.A A.A 16 A C. V. Raman Global University, Odisha Cyclooctatetraene is supposed to be antiaromatic but because of the nonplanar structure, it is non-aromatic.
16-12-2020 17 C. V. Raman Global University, Odisha Tropone is aromatic due to electron withdrawing nature of carbonyl group and system will be conjugated with positive charge of carbonyl carbon with 6 pi-electrons.
16-12-2020 18 C. V. Raman Global University, Odisha Pyrrole and Pyridine
16-12-2020 19 C. V. Raman Global University, Odisha 16-12-2020 20 https://chem.libretexts.org/Courses/Purdue/Purdue%3A_Chem_26200%3A_Organic_Chemistry_II_(Wenthold)/Chapter_14.__Aromaticity/1C. V. Raman Global University, Odisha 4.04%3A_MO_description_of_aromaticity 16-12-2020 21 https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Map%3A_Organic_Chemistry_(McMurry)/C. V. Raman Global University,15% 3OdishaA_Benzene_and_Aromaticity/ 15.06%3A_Aromatic_Heterocycles-_Pyridine_ Furan
16-12-2020 22 C. V. Raman Global University, Odisha Annulene Annulenes are monocyclic compounds with alternative single and double bonds.
[4n] annulene = Antiaromatic
[4n+2] annulene = Aromatic
16-12-2020 23 C. V. Raman Global University, Odisha Annulene
[10] annulene is supposed to be aromatic but because of close proximity between the 2H’s ring can’t remain in one plane.
[10] annulene is non-aromatic and called as puckering of the ring.
16-12-2020 24 C. V. Raman Global University, Odisha Homoaromatic
In a molecule, if delocalization of π cloud or π conjugation by passes sp3 atoms of ring & possess Aromaticity called homoaromatic molecule.
16-12-2020 25 C. V. Raman Global University, Odisha 16-12-2020 26 C. V. Raman Global University, Odisha Cyclodextrins
Cyclodextrins are macrocyclic oligosaccharides containing at least six D-(+)- glucopyranose units attached by α (1-4) bonds.
One of the important feature of cyclodextrins is their ability to form inclusion complexes with a variety of compounds, by entrapping their molecules inside the cyclodextrin cavity, which act as a host.
The smallest cyclodextrin is α-cyclodextrin which has a diameter about double to that of 18-crown-6.
16-12-2020 27 C. V. Raman Global University, Odisha The complex formed results-
Increased solubility
Increased dissolution rate
Increased stability
Decreased volatility
Cyclodextrin are relatively hydrophobic central cavity and hydrophilic outer surface.
16-12-2020 28 C. V. Raman Global University, Odisha 16-12-2020 29 https://www.youtube.com/watch?v=yDyhBEUKqcU C. V. Raman Global University, Odisha Types of Cyclodextrin α -cyclodextrin: 6 membered sugar ring molecule Relatively irritating after Intramuscular injection Binds lipids.
16-12-2020 30 C. V. Raman Global University, Odisha Types of Cyclodextrin β-cyclodextrin: 7 membered sugar ring molecule Relatively less irritating after Intramuscular injection Binds cholesterol.
16-12-2020 31 C. V. Raman Global University, Odisha Types of Cyclodextrin γ-cyclodextrin: 8 membered sugar ring molecule
16-12-2020 32 C. V. Raman Global University, Odisha 16-12-2020 33 C. V. Raman Global University, Odisha Characteristics-
It is a white in colour
Practically odorless
Fine crystalline powders
Slightly sweet taste
It is chemically inert
16-12-2020 34 C. V. Raman Global University, Odisha Synthesis- The production of cyclodextrin is relatively simple and involves treatment of ordinary starch with a set of enzymes.
Commonly cyclodextrin glucosyltransferase (CGTase) is employed along with α- amylase.
First starch is liquefied either by heat treatment or using α-amylase, then CGTase is added for the enzymatic conversion.
CGTases can synthesize all forms of cyclodextrins.
16-12-2020 35 C. V. Raman Global University, Odisha Inclusion Complex - Internal hydrophobic cavity is the key feature for complex formation.
Inclusion complex formation can be regarded as encapsulation of drug molecule or at least part of molecule.
16-12-2020 36 C. V. Raman Global University, Odisha 16-12-2020 37 C. V. Raman Global University, Odisha Modifications-
Cyclodextrin R R Molecular Wt. Solubility (D) (mg/ml)
2-HP-β-CD -CH2CHOHCH3 1400 600
SBE-β-CD -(CH2)4SO3 2163 500
RM-β-CD -CH3 1312 500
16-12-2020 38 C. V. Raman Global University, Odisha Catenanes and Rotaxanes Rotaxanes and catenanes are structurally interlocked molecules in which there is no covalent connection between the components of each system.
16-12-2020 39 C. V. Raman Global University, Odisha 16-12-2020 40 C. V. Raman Global University, Odisha Synthesis of Catenanes and Rotaxanes
Pseudorotaxane is the basic structure for the synthesis of both Catenanes and Rotaxanes.
16-12-2020 41 C. V. Raman Global University, Odisha 16-12-2020 42 C. V. Raman Global University, Odisha Thank You
Dr. L. Satish K. Achary
Department of Chemistry
Mail: [email protected]
Contact: 9438563012
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