Pages: 8

This chapter discusses the importance of electron movement in understanding organic chemistry. This chapter focuses on studying the basics of how to write a reasonable reaction mechanism. Initially, an electronic configuration is discussed. The main question this chapter deals with is how a chemical reaction occurs. The various parameters like ease of electron donation, ease of electron acceptance, polarization of bonds, and so on are discussed. The later part of the chapter deals with some of the common errors to avoid, rules to remember in the deconstruction of chemical reactions, what is heterolytic cleavage, how we can apply arrow-pushing mechanism to amide hydrolysis (under acidic and basic conditions), and cyanide hydrolysis under acidic and basic conditions.

Pages: 6

This chapter deals with geometric isomerism. Initially, the criterion for geometrical isomerism is discussed. It is followed by classifying various types of isomerism by connectivity, rotation about bonds, and optical activity. Unlike simple systems (similar groups) to identify cis-trans isomers, the criteria to identify cis-trans isomerism where all the four groups are different require learning about the CIP rule. Based on atomic number how to assign priority and how to determine E/Z isomer is given with suitable examples. Cis-trans isomerism in heteroatom double bonds and captodative ethylenes are also discussed. After studying the open chain systems, the cis-trans isomerism in cyclic systems, mainly cycloalkanes (3, 5, and 6 membered), and cis- and trans-decalins are covered. This chapter concludes with a study of molecular electrical potential surfaces of cis and trans isomers and application of geometric isomerism.

Pages: 16

In this chapter, some basic topics like the nature of electrons, shapes of orbitals, 2D representation of 3D molecules, Sawhorse representation, Newman projection, and Fischer projection are covered in the beginning. Interconversion of Sawhorse and Fischer projection are also discussed. The study of conformational isomerism in acyclic systems comprises learning about rotational barrier and how it affects ethane and simple alkanes. It is followed by familiarizing Klyne–Prelog notations (syn, anti, peri, clinal arrangements with respect to the dihedral angle). Potential energy diagrams for various conformations of ethane and butane followed by rotational energy barriers for other simple systems are covered. The study about conformational analysis of acyclic systems includes the Fluorine gauche effect and allylic strain effect. Later, conformational analysis of cyclic systems, including angle strain or Baeyer strain, limitations of Baeyer theory, angle strain for various ring systems, heat of combustion in cycloalkanes, and total strain in cycloalkanes, is discussed. In cycloalkanes, the topics covered cyclopropane (bonding, NMR, and reactivity), cyclobutene, cyclopentane, and cyclohexane. Conformational analysis of cyclohexane, axial and equatorial bonds, 1,3-diaxial interaction, A-value of various substituents, and transannular or Prelog strain (steric strain) are also covered.

Pages: 9

An important topic in organic chemistry is stereochemistry. In this chapter, the importance of stereochemistry and symmetry is introduced in the beginning. To understand stereochemistry, some basic concepts like linear symmetry, point symmetry, and radial symmetry are briefly discussed. Two conventions used for symmetry (Schoenflies and Hermann–Mauguin notation), various symmetry elements, and symmetry operations are explained. Interrelationships between the symmetry elements and point group are also presented. Point group classification and how to identify point groups are described. To understand the point group classifications, examples like ethane, ethanol, and 1,2-ethanediol (staggered and eclipsed) are discussed. Finally, axial chirality or atropisomerism, and planar chirality with few examples are given.

Pages: 13

After learning the basics of stereochemistry, this chapter exposes the reader to understand some relationship between chirality and smell and taste. To learn and represent chemical transformations, many stereochemical conventions like erythro and threo, D-L notation or Fischer notation, alpha-beta arrangements, cis and trans or syn and anti, and exo and endo are explained. It is important to unambiguously represent chiral molecules, for which R-S nomenclature is generally used. By using Cahn–Ingold–Prelog rules, how R-S notation can be assigned with suitable examples is demonstrated. Helical chirality descriptors (like plus and minus), Re-Si faces in a molecule are explained with suitable examples. To identify and assign Re-Si faces, reactions like hydride ion attack and bromide ion attack are provided. The topicity (homotopic, enantiotopic, diastereotopic) of a molecule can be identified using the substitution test for equivalence of hydrogen. Suitable examples are given to learn what are diastereomers and what are enantiomers in acyclic and cyclic systems. Finally, meso compounds are briefly discussed.

Pages: 10

After learning about stereochemical notations, enantiomers, and diastereomers, it is necessary to learn how to experimentally identify chirality. To do that, it is essential to learn what are plane, circularly and elliptically polarized light, and the functioning of polarimeter. How linear and circularly polarized lights are related to circular dichroism (CD) and optical rotatory dispersion (ORD) are explained. The difference between circular and linear birefringence and the comparison between birefringence and optical activity are discussed briefly. Later, Cotton effect, types of Cotton effect curves, applications of ORD measurements to steroidal ketones, axial halo ketone rule, advantages and limitations of ORD and CD, and application of CD are discussed. Finally, the chapter ends with the determination of absolute configuration based on methods related to chemical correlation, diastereomers, chiral center, correlation, and resolution.

Pages: 9

This chapter starts with explaining types of stereochemical reactions, mainly stereoselective and stereospecific reactions. Some examples of stereospecific reactions include inversion (Mitsunobu reaction) and retention (neighboring group participation). Some of the basic misconception related to retention is demystified. Further additional stereochemical reactions with detailed mechanisms discussed include the addition of bromine to alkenes (anti-addition), epoxidation of alkene (syn addition), and hydroboration–oxidation of alkenes (cis addition). Acyclic and cyclic stereoselection, asymmetric induction models, Cram’s model (ketone reduction with lithium aluminum hydride, the Grignard addition to the aldehyde), the Felkin Ahn model, and Prelog rule are a few other topics that are discussed with examples.

Pages: 9

A brief introduction to aromatic chemistry starts with studying some important features of aromatic compounds. They include criteria for aromaticity. To understand the unusually low reactivity of benzene toward addition and the existence of resonance stabilization energies, specific studies related to the heat of hydrogenation of various cycloolefins are carried out. Other topics that will be covered include aromatic ring current, Musulin–Frost circle, deviations of aromatic criteria, non-aromatic, and anti-aromatic compounds. As an extension, polycyclic aromatic hydrocarbons (PAHs), ortho and peri fusion (cluster), and applications of PAH are given. Polyacenes and their unique properties are discussed. Finally, six-membered aromatic heterocycles, other monocyclic ring systems (6 π electrons) bicyclic ring systems, annulene, homoaromatic compounds, Baird’s rule, and Möbius aromaticity are covered.

Pages: 23

After gaining some understanding of what are aromatic compounds, in this chapter, their reactivity is discussed. This chapter begins with types of electrophilic substitutions and how they occur (charge transfer or π complex and σ Complex or Wheland intermediate). Various electrophilic substitutions like nitration, halogenation, sulfonation, Friedel–Crafts alkylation, limitations of Friedel–Crafts alkylation, Friedel–Crafts acylation and their mechanisms, and Gattermann–Koch reaction are discussed with suitable examples. Later, electrophilic substitution of substituted benzenes (orientation) is covered. It is followed by another class of reactions, namely, aromatic nucleophilic substitution. Here, two types of aromatic nucleophilic substitution mechanisms, namely, the addition–elimination mechanism and elimination–addition mechanism, are discussed. Additional topics related to the Chichibabin reaction, Meisenheimer complex, and Sanger reaction are also provided for better understanding. Finally, ipso, cine, and tele substitutions, vicarious substitution, meso substitution, peri substitution, σH adducts in nucleophilic substitution, SNAr vs Oxidative nucleophilic substitution are discussed.

Pages: 23

Understanding and mastering organic chemistry require knowledge of how reactions occur. To address this, important parameters that influence a chemical reaction, namely, kinetic and thermodynamics, are discussed in this chapter. It starts with a reaction coordinate diagram, free energy and activation energy, kinetic and thermodynamic controlled reactions, and types of mechanism (bonds breaking). This is followed by learning about Hammond postulate, and the application of this postulate to SN1 reaction (transition states), electrophilic substitution of benzene, and limitations of Hammond postulate. Another important topic is the linear free energy relationship. Here the topics covered include derivation of the Hammett equation, the applicability of the Hammett equation, substituent constants (σ), σ and electron-withdrawing group (EWG)/electron-donating group (EDG), reaction constant (ρ), ρ and EWG/EDG and application of Hammett equation. Many theories have exceptions, and Hammett’s equation is no exception. The topics related to discrepancies in Hammett equation (concave upwards, concave downwards) and Taft equation are discussed. Finally, Curtin–Hammett principles are discussed. Here the description of Curtin–Hammett equation, transition state energy vs stability, and various cases related to different scenarios (more stable isomer/conformer reacts faster, less stable isomer/conformer reacts faster, each isomer/conformer reacts at a similar rate) are covered with suitable examples.

Pages: 25

This chapter and a few subsequent ones are devoted to understanding and predicting chemical reactions through reactive intermediates. The first one is carbocations. This chapter begins with notations to represent substituents (C, Z, and X), types, and generation of carbocations (heterolytic fission, addition of cations to neutral species, from other cations). It is followed by a brief discussion about the structure and geometry of carbocations. Later, the stability of carbocations (tert-butyl), non-benzenoid aromatic carbocations, carbocation stabilizing groups (benzyl, heteroatom), carbocation destabilizing groups, and hyperconjugation is discussed. Briefly, non-classical carbocations are explained. It is followed by the study of carbocation reactions (substitution with nucleophile, elimination of proton, addition to multiple bonds, in terpene synthesis) with suitable examples. Another important set of reactions, namely, rearrangement reactions, are elaborately discussed. Some of the types of reactions, including no change in carbon skeleton (1,2-hydride ion shift and allyl rearrangement), change in carbon skeleton (Neopentyl rearrangement, Wagner–Meerwein shift, Pinacol–Pinacolone rearrangement), loss of groups (Wolff rearrangement), rearrangement involving hetero atom (Hofmann rearrangement Lossen, Curtius, Schmidt reactions, Beckmann rearrangement, Baeyer–Villiger oxidation), and finally anchimeric assistance, are covered.

Pages: 21

Organic reactions involve the movement of electrons, and most of the reactions can be classified as redox reactions or acid–base reactions. We can use the acid dissociation constant and hence we can associate pKa with all the functional groups. In this chapter, we will study about parameters that affect pKa (inductive effect, electronegativity, resonance stabilization, electron-withdrawing effect, hybridization, and attaining aromaticity). A small section is devoted to hard and soft acids and bases principles. It is followed by understanding the structure of carbanion and the formation of carbanion (deprotonation organometallics – lithium bases and decarboxylation of carboxylate anion). Another important factor that affects carbanion is the substituents. The effect of substituents on the stability of carbanions (inductive effect, resonance, electronegativity/dipolar, electron-donating and electron-withdrawing groups, and hybridization) is discussed with suitable examples. Lastly, carbanion reactions like acyl anions (Benzoin condensation), rearrangements (Benzilic acid and Favorskii) umpolung or the inversion of reactivity through the formation and application of dithanes, and the reaction of dithianes and Henry reaction are covered.

Pages: 19

The next intermediate is free radicals. A brief information about bond dissociation energies followed by the formation of free radicals (thermal decomposition, photolysis, redox reactions, and electrochemical methods) is given. It is followed by topics related to the structure and stereochemistry of radicals. A small section is devoted to understanding the anomalous behavior of halo-substituted radicals. Factors that affect radical stability (conjugation, hybridization, hyperconjugation, and captodative effect) are discussed. Kinetic stabilization that influences the reactivity of free radicals is briefly covered. Steps involved in free radical chain reactions, the polar nature of radicals, atom electronegativity and philicity of radicals, cation and anion stability are covered separately. Another major area is free radical reactions. Here atom abstraction, intermolecular hydrogen abstraction, bromination, radical addition, fragmentation reactions, single electron transfer, and disproportionation reactions are covered. Radical cyclization and rules governing this (Baldwin’s rules) are briefly discussed. Finally, various free radical reactions (anti-Markovnikov addition, Giese reaction, Hofmann–Löffler–Freytag reaction, Barton decarboxylation, Barton–McCombie deoxygenation, Wohl–Ziegler bromination, Birch reduction, and Sandmeyer reaction) are discussed with suitable examples.

Pages: 7

This chapter starts with another reactive intermediate namely carbenes, which can also form new carbon−carbon bonds. There are two major types of carbenes which are singlet and triplet carbenes. Many similarities and differences between them are briefly discussed. Stabilization of carbenes by complexation with transition metals and substituent’s effect on carbenes are discussed. It is followed by the generation of carbenes where 1,1 α-elimination and diazo decompositions are mentioned. Later, the stability of carbenes is covered. Other topics that are discussed include the reactivity of carbenes, stereochemistry of carbene reactions, Simmons–Smith reaction, electrophilic carbene, nonstereospecific addition of a carbene, and rearrangements (alkene formation, ring expansion). Finally, nitrenes their formation and reactions (Wolff rearrangement) are covered.

Pages: 31

This chapter covers important topics related to carbon–carbon bond formation using carbon nucleophiles. It starts with some basic information related to the comparison of C=C and C=X (X = O, N, and S), nucleophilic addition vs substitution of carbonyl groups, types of carbonyl addition reactions (Class e and Class n reactions), mechanism of base-catalyzed hydration, examples of carbonyl addition reactions (addition of alcohols, thiols, amines, hydride, and alkoxide to aldehydes and ketones), carbonyl addition with active methylene compounds, and base-catalyzed condensation reactions (Cannizzaro reaction, Grignard reaction). This is followed by studying enolate anions (acid- and base-catalyzed halogenation of carbonyl compounds), haloform reaction, stereochemical outcome of enolization, choice of base, steric effect on enolate formation, and nature of the base regioselectivity in enolate formation. A few reactions related to enolates are also covered. Next, enamines are included. Comparison between imines and enamines, resonance structure of enamines, evidence for enamines, formation, and reactions of enamines are covered. Finally, enol ethers are discussed. Their formation and reactions, chemoselectivity, regioselectivity, C vs O-acylation, and cyclopropanation of silyl enol ethers are a few topics that are covered.

Pages: 11

In the final chapter few name reactions are covered. A very brief overview of a few reactions that generate chiral centers (asymmetric hydrogenation of C=C, cyanation of C=O, asymmetric epoxidation of C=C) is given. This chapter starts with a Nobel-winning reaction called Sharpless epoxidation. In this reaction, absolute configurations of newly formed epoxy alcohols can be easily assigned purely based on the facial selectivity rule (use of + and – isomers of tartrate). Sharpless epoxidation, its advantages, and stereospecificity are a few topics that are included. It is followed by another Nobel-winning reaction called click reactions. Here is a brief information about azide-alkyne cycloaddition reaction and copper-catalyzed azide-alkyne cycloaddition. Finally, another important and well-known Nobel reaction, the Diels–Alder reaction is discussed. Importance of the DAR, its stereospecificity and regioselectivity, simple rules governing Diels–Alder reaction, exo and endo naming, stereochemistry of diene and dienophile, regioselectivity (ortho/para) model, Frontier molecular orbital interactions are few topics that are covered.