Chemical reactions are the basics of Organic Chemistry. They enable the transformation of molecules for various applications in pharmaceuticals, materials science, and biochemistry. Among the fundamental reaction types, substitution, elimination, and addition reactions are particularly significant due to their role in molecular modifications and synthesis. Substitution reactions involve replacing one atom or group in a molecule with another. It is often observed in halogenated organic compounds. Elimination reactions form unsaturated compounds by removing atoms or functional groups, playing a crucial role in producing alkenes and alkynes. Addition reactions, conversely, involve the direct combination of reactants to form a more complex product, commonly observed in alkene and alkyne chemistry. Understanding these reactions and mechanisms is essential to designing and synthesizing new materials and drugs. They are indispensable in both academic research and industrial applications. In this article, we will explore the main chemical reactions in Organic Chemistry.l.toLowerCase().replace(/\s+/g,"-")" id="c257c1b1-bc6d-4eb9-9e57-dde420f55ea7" data-toc-id="c257c1b1-bc6d-4eb9-9e57-dde420f55ea7">1. Addition ReactionAn addition reaction combines two reactants to form a product, typically involving alkenes and alkynes.Example: Electrophilic Addition of HBr to an AlkeneMechanism:The double bond in ethene (CH2=CH2) donates electrons to H⁺ from HBr, forming a carbocation intermediate.The first step involves the Br⁻ ion attack on the positively charged carbon. It leads to the formation of bromoethane (CH3CH2Br).This reaction follows Markovnikov's rule. According to this rule, the electrophile (H⁺) adds more hydrogen atoms to the carbon. l.toLowerCase().replace(/\s+/g,"-")" id="e226d270-a7b7-4b9e-a38a-dd030fa9443f" data-toc-id="e226d270-a7b7-4b9e-a38a-dd030fa9443f">2. Substitution ReactionsChemical reactions where another atom or group replaces an atom or group in a molecule are known as Substitution reactions. These reactions are significant and common in organic chemistry. They have a crucial role in alkyl halides and aromatic compounds. The nucleophilic substitution and electrophilic substitution are two key types of substitution reactions. Each is characterized by the nature of the attacking species (nucleophile or electrophile) and the substrate.l.toLowerCase().replace(/\s+/g,"-")" id="c73746a5-19c0-439c-93b5-32941675ca32" data-toc-id="c73746a5-19c0-439c-93b5-32941675ca32">Types of Substitution ReactionsA. Nucleophilic Substitution Reactions (SN1 and SN2)B. Electrophilic Substitution Reactionsl.toLowerCase().replace(/\s+/g,"-")" id="bd6d4f61-7715-4194-921f-08d5074d6b49" data-toc-id="bd6d4f61-7715-4194-921f-08d5074d6b49">A. Nucleophilic SubstitutionNucleophilic substitution reactions involve the replacement of a leaving group by a nucleophile. These reactions are often seen in aliphatic organic compounds such as alkyl halides. SN1 and SN2 are two primary mechanisms by which nucleophilic substitution are given below;i. SN1 (Unimolecular Nucleophilic Substitution)The SN1 mechanism proceeds in two steps:Step 1: The leaving group departs from the substrate. It immediately forms a carbocation intermediate. This is the rate-determining step, as it involves breaking a bond and requires energy.Step 2: The nucleophile attacks the carbocation, forming the product.FOR EXAMPLE:(CH3)3CBr + H2O → (CH3)3COH + HBrA classic example of an SN1 reaction is the hydrolysis of tert-butyl bromide (or chloride), where the tertiary carbon atom readily forms a stable carbocation, allowing the water molecule to attack and produce tert-butyl alcohol; this reaction occurs in a two-step process with the first step being the rate-determining step where the leaving group departs, forming the carbocation.MechanismStep 1 (Slow): The carbon-bromine bond breaks heterolytically, with the bromine leaving as a bromide ion, generating a tert-butyl carbocation. (CH3)3C-Br → (CH3)3C+ + Br-Step 2 (Fast): A water molecule (acting as a nucleophile) attacks the planar carbocation from either side, forming a protonated alcohol.(CH3)3C+ + H2O → (CH3)3C-OH2+Final step: The protonated alcohol loses a proton to a solvent molecule, yielding the final product, tert-butyl alcohol. (CH3)3C-OH2+ + H2O → (CH3)3C-OH + H3O+MECHANISMStep 1: Formation of tert-butyl carbocation by separating a bromide anion from the carbon atom of tert-butyl bromide.Step 2: Nucleophilic attack of the carbocation by a water molecule, resulting in an oxonium ion intermediate.Step 3: Deprotonation of the protonated nucleophile by a second water molecule, which acts as a base, resulting in an alcohol and a hydronium ion.The relative reactivity of alkyl halides towards SN1 reaction:Tertiary 30 > Secondary 20 > Primary 10 > Methyl ii. SN2 (Bimolecular Nucleophilic Substitution)The SN2 mechanism occurs in a single concerted step, where the nucleophile attacks the substrate and the leaving group departs simultaneously.FOR EXAMPLE:CH3Br + OH- → CH3OH + Br-The hydrolysis of methyl bromide is a classic example of an SN2 (bimolecular nucleophilic substitution) reaction, where the hydroxide ion (OH-) acts as the nucleophile, attacking the carbon atom in methyl bromide (CH3Br) from the backside, simultaneously breaking the carbon-bromine bond and forming a new carbon-oxygen bond, resulting in methanol (CH3OH) and a bromide ion (Br-) as products; this occurs in a single concerted step with inversion of stereochemistry.Step 1 (concerted): The hydroxide ion (OH—) approaches the carbon atom of methyl bromide from the back side, forming a transition state in which the carbon is partially bonded to both the incoming OH—and the leaving Br-.Step 2 (product formation): The carbon-bromine bond breaks completely, and the carbon-oxygen bond fully forms, resulting in methanol and a bromide ion. MECHANISMFigure: SN2 reaction mechanism between methyl bromide and hydroxide. The figure shows nucleophile attacks from the back side, 1800 away from the leaving group.The relative reactivity of alkyl halides towards SN2 reaction:Methyl > Primary 10 > Secondary 20 > Tertiary 30 too reactive to undergo SN2 reactionCOMPARISON OF SN1 AND SN2PropertiesSN1SN2Rate LawUnimolecular(substrate only)Bimolecular(Substrate and nucleophile)Big BarrierCarbocation stabilitySteric HindranceAlkyl Halide (Electrophile)Nature30 (fast) > 20 > 10 (slowest)10 (fast)> 20 > 30NucleophileWeak generally neutralStrong generally bearing a negative chargeSolventPolar protic, e.g., water, alcoholPolar aprotic, e.g., DMSO, acetoneStereochemistryA mix of retention and inversion100% inversionl.toLowerCase().replace(/\s+/g,"-")" id="2a734f08-5799-4280-9e3c-5916c2098be8" data-toc-id="2a734f08-5799-4280-9e3c-5916c2098be8">B. ELECTROPHILIC SUBSTITUTIONAn electrophilic substitution reaction is a chemical reaction in which an electrophile (a positively charged species) replaces a hydrogen atom on an aromatic ring, like benzene, while preserving the molecule's overall aromaticity.FOR EXAMPLE: Nitration of BenzeneA typical example is the nitration of benzene, where a nitro group (NO2+) substitutes a hydrogen atom on the benzene ring, forming nitrobenzene; the mechanism involves the electrophile attacking the electron-rich aromatic ring, creating a positively charged intermediate (called a sigma complex), and then losing a proton to regain aromaticity.Mechanism:Generation of the Electrophile: In the first step, the nitric acid reacts with sulfuric acid to generate the nitronium ion (NO2+), which acts as the electrophile.HNO3 + 2H2SO4 → NO2+ + H3O+ + 2HSO4-1. Attack on the Aromatic Ring: The nitronium ion attacks the electron-rich benzene ring, forming a positively charged intermediate (sigma complex) where one carbon is sp3 hybridized, disrupting the aromaticity temporarily.2. Loss of Proton: The sigma complex regains aromaticity by losing a proton (H+) to a base like HSO4- in the reaction mixture, forming nitrobenzene.MECHANISM1- Generation of nitronium ion2- Attack of aromatic ring and loss of protonl.toLowerCase().replace(/\s+/g,"-")" id="5a915e28-d748-4fe1-8277-c5764b259ee4" data-toc-id="5a915e28-d748-4fe1-8277-c5764b259ee4">3. ELIMINATION REACTIONSThese reactions are crucial for organic chemistry. In these reactions, double or triple bonds are formed by eliminating two atoms or groups from the molecules. These reactions contrast with addition reactions, where atoms are incorporated into a molecule. They are particularly significant in organic synthesis, especially for creating alkenes and alkynes.l.toLowerCase().replace(/\s+/g,"-")" id="48ce6b95-17e1-48e3-8943-fa1ce8ed12a7" data-toc-id="48ce6b95-17e1-48e3-8943-fa1ce8ed12a7">Types of Elimination ReactionsElimination reactions can proceed through different mechanisms depending on the reaction conditions and the nature of the reactants. The following are the two main types of elimination reactions:A. E1 (Unimolecular Elimination) ReactionB. E2 (Bimolecular Elimination) ReactionA. E1 Reaction (Unimolecular Elimination)The E1 (unimolecular elimination) mechanism occurs in two distinct steps:1. Formation of a Carbocation: The first step involves the loss of a leaving group, such as a halide ion, which forms a positively charged carbocation intermediate.2. Proton Elimination: A base then abstracts a proton from a neighboring carbon, leading to the formation of a double bond and the generation of an alkene.The stability of carbocation determines the rate of alkyl halide E1 reactions. Hence, the order of reactivity of alkyl halides in the E1 reaction is:30 haloalkane > 20 haloalkane > 10 haloalkaneKinetics of E1 reaction:The rate of formation of alkene in E1 reactions is decided by alkyl halide concentrations, which follow first-order kinetics.Rate α [Alkyl halide]R = k [RX]Characteristics of the E1 Reaction:· The first step involves the elimination of leaving the group. This step decides the rate of reactions.· It follows first-order kinetics, meaning the rate depends solely on the concentration of the substrate.· It proceeds best with tertiary substrates, as tertiary carbocations are more stable than secondary or primary carbocations.· .Rearrangement in the carbocation intermediate occurs, and this rearranging leads to the formation of stable products.B. E2 Reaction (Bimolecular Elimination)The E2 (bimolecular elimination) reaction occurs in a single concerted step, meaning that bond breaking and bond forming happen simultaneously.l.toLowerCase().replace(/\s+/g,"-")" id="1ced2522-1824-4328-9549-e66aef47d1cc" data-toc-id="1ced2522-1824-4328-9549-e66aef47d1cc">Mechanism of E2 Reaction:1. The strong base abstracts a proton from the β-carbon. The β- carbon is adjacent to the carbon bearing the leaving group.2. As the proton is removed, the electrons form a new double bond between the α and β carbon atoms.3. Simultaneously, the leaving group departs from the molecule, resulting in the formation of an alkene.l.toLowerCase().replace(/\s+/g,"-")" id="313da724-81c1-4274-98fc-ab47c31f6ebf" data-toc-id="313da724-81c1-4274-98fc-ab47c31f6ebf">Key Features of the E2 Reaction:· It follows second-order kinetics, meaning that the reaction rate depends on the substrate and the base concentration.· No carbocation intermediate is formed.· A strong base is generally required for the reaction to proceed efficiently.· The leaving group and the hydrogen being removed must be anti-periplanar, meaning they are positioned in opposite planes for optimal orbital overlap.Kinetics of E2 Reaction :In the E2 reaction, the rate of dehydrohalogenation (alkyl halide and base concentrations decide the rate of formation of alkene) follows second-order kinetics.Rate α [Alkyl halide] [Base]R = k[RX] [:B]FactorsE1E2Rate LawUnimolecular Bimolecular Substrate StructureE1 reactions favor tertiary substrates, where stable carbocations are formed, whereas E2 reactions can occur with primary, secondary, or tertiary substrates, but their rate increases with the substrate's bulkiness.E2 reactions can occur with primary, secondary, or tertiary substrates, but the rate increases with substrate bulk. Base Strength :Weak bases (like CH3OH or C2H5OH) mostly gives E1 reactionsThese reactions are favored by strong bases, e.g., CH3O-, OH-Leaving Group:A good leaving group (like halides Cl⁻, Br⁻, and I⁻) enhances the reaction rate in both E1 and E2.A good leaving group (like halides Cl⁻, Br⁻, and I⁻) enhances the reaction rate in both E1 and E2.SolventPolar protic solvents facilitate E1 reactions by effectively stabilizing the intermediate carbocation.Aprotic solvents are favored in E2 reactions since they minimize the stabilization of the nucleophile or Base, thereby enhancing its reactivity.l.toLowerCase().replace(/\s+/g,"-")" id="c889dc16-a477-401b-8af7-8e5a87868d8e" data-toc-id="c889dc16-a477-401b-8af7-8e5a87868d8e">4. RADICAL REACTIONA radical reaction is an organic reaction involving the formation and interaction of free radicals—highly reactive species with unpaired electrons. These reactions typically proceed via a chain mechanism involving three fundamental steps: initiation, propagation, and termination. Radical reactions are significant in various organic transformations, including halogenation, polymerization, and oxidation.l.toLowerCase().replace(/\s+/g,"-")" id="3cb93335-1762-475f-ad2b-ba9e459bb140" data-toc-id="3cb93335-1762-475f-ad2b-ba9e459bb140">Characteristics of Radical Reactions1. Homolytic Bond Cleavage: Radicals are formed via homolysis, where a covalent bond breaks evenly, and each atom retains one electron.2. Highly Reactive Intermediates: Radicals are unstable and seek to pair their unpaired electrons, making them highly reactive.3. Chain Process: Radical reactions usually proceed cyclically, with intermediate radicals regenerating new radicals.4. Influence of Light, Heat, or Peroxides: Radical reactions often require initiation sources like UV light, heat, or radical initiators like peroxides.l.toLowerCase().replace(/\s+/g,"-")" id="2dfb8256-93f2-4d9b-9cd0-1c8b7c606013" data-toc-id="2dfb8256-93f2-4d9b-9cd0-1c8b7c606013">Example: Halogenation of AlkanesOne of the most well-known radical reactions is the chlorination of methane (CH₄) with chlorine (Cl₂) under UV light to produce chloromethane (CH₃Cl). The reaction follows a chain mechanism.l.toLowerCase().replace(/\s+/g,"-")" id="f2cb1c2c-0274-401d-9feb-e5cef3d72b2e" data-toc-id="f2cb1c2c-0274-401d-9feb-e5cef3d72b2e">Mechanism of Radical HalogenationThis reaction occurs in three key stages:l.toLowerCase().replace(/\s+/g,"-")" id="b3a9f565-3883-40e6-a59f-b8efe2670e70" data-toc-id="b3a9f565-3883-40e6-a59f-b8efe2670e70">1. Initiation Step: The Cl–Cl bond undergoes homolytic cleavage under UV light, forming chlorine radicals:Cl2 hv → 2Cl∙Each chlorine radical (Cl·) possesses an unpaired electron, making it highly reactive.l.toLowerCase().replace(/\s+/g,"-")" id="f41d5d6f-15e7-4350-adb1-bdf19d00e6eb" data-toc-id="f41d5d6f-15e7-4350-adb1-bdf19d00e6eb">2. Propagation StepsIn this stage, a chain reaction is established:Step 1: Hydrogen abstraction from methaneA chlorine radical reacts with methane (CH₄), abstracting a hydrogen atom and forming a methyl radical (CH₃·):Cl∙ + CH4 → CH3∙ + HClStep2: Chlorine addition to methyl radicalThe methyl radical then reacts with a chlorine molecule (Cl₂), forming chloromethane (CH₃Cl) and generating another chlorine radical:CH3∙ + Cl2 → CH3Cl + Cl∙The cycle continues since a new chlorine radical is formed, making it a chain reaction.l.toLowerCase().replace(/\s+/g,"-")" id="af4a6b0b-aadc-43a1-91c7-9dc7f2b134c1" data-toc-id="af4a6b0b-aadc-43a1-91c7-9dc7f2b134c1">3. Termination StepThe reaction stops when radicals combine, neutralizing their unpaired electrons. Possible termination reactions include:Cl∙ + Cl∙ → Cl2CH3∙ + Cl∙ → CH3ClCH3∙ + CH3∙ → C2H6These termination steps prevent further radical propagation and complete the reaction.l.toLowerCase().replace(/\s+/g,"-")" id="32e55a7b-9607-4b6e-8704-5534ec5420cb" data-toc-id="32e55a7b-9607-4b6e-8704-5534ec5420cb">Conclusion:In organic chemistry, addition, elimination, and substitution reactions are key in modifying organic compounds. Addition reactions occur when two or more molecules combine to form a larger product. They typically occur in unsaturated compounds like alkenes and alkynes. In contrast, elimination reactions involve the removal of atoms or groups from a molecule, leading to the formation of double or triple bonds. They are often producing alkenes or alkynes. Substitution reactions, however, replace one atom or functional group in a molecule with another. They are commonly observed in saturated hydrocarbons and aromatic compounds. These fundamental reactions are essential for creating complex molecules, analyzing reaction pathways, and predicting chemical outcomes. A strong understanding of these processes is vital for progress in pharmaceuticals, materials science, and industrial chemistry.