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Organic Chemistry - Nucleophilic Substitution Reactions

Student Learning Objectives (SLOs)

  • Naming Alkyl Halides:

    • Familiarize with IUPAC rules for naming.

  • Leaving Group Ability:

    • Understand and rank halogens by their ability to act as leaving groups.

  • Electrophile Substitution:

    • Impact on SN1 and SN2 rates of reaction.

  • Nucleophilicity Factors:

    • Study sterics, charge, and electronegativity that affect nucleophilicity.

  • Solvent Effects:

    • Analyze how solvents influence substitution reactions.

  • Reaction Mechanisms:

    • Illustrate SN1 and SN2 mechanisms using curved arrows and reaction coordinate diagrams, focusing on stereochemistry implications.

  • Determine Mechanisms:

    • Assess when SN1 or SN2 will occur based on reactants and conditions.

  • Predict Substitution Reactions:

    • Identify reactants leading to specified products in substitution reactions.

Organic Reactions Overview

  • Essence of Organic Chemistry:

    • Organic reactions stem from bonds broken and formed at functional groups, influenced by electron-rich or deficient sites in reacting molecules.

  • Reaction Steps:

    • Differentiate between single-step and multi-step reactions.

Writing Reactions

  • General Principles:

    • Indicate solvents and temperature above or below the reaction arrow.

    • Use "hν" for light-required reactions and "Δ" for heat.

  • Sequential Reactions:

    • Number the steps above or below reaction arrows to denote the sequence.

Types of Reactions

  • Substitution Reactions:

    • General form: Y replaces Z on a carbon atom.

  • Elimination Reactions:

    • Elements from the starting material are lost, forming a π bond.

  • Addition Reactions:

    • Introducing elements into the starting material.

  • Relationship of Addition and Elimination:

    • They are opposite reactions; elimination involves bond formation, and addition involves bond breaking, often reversible.

Energy Diagrams

  • Definition:

    • Energy diagrams represent energy changes during reactions (y-axis energy vs. x-axis reaction progress).

  • Transition State and Activation Energy:

    • The difference in energy between reactants and products is represented as ΔH°.

    • The energy barrier called Ea must be surpassed for reactions to proceed.

    • Greater Ea indicates slower reaction rates.

Detailed Transition State Characteristics

  • Structure:

    • Representative of a point between reactants and products, shown with dashed lines for partially formed/broken bonds.

  • Notation:

    • Depicted in brackets with a superscript double dagger (‡).

Energy Diagrams for Reactions

  • Slow Endothermic Reaction:

    • High E_a, indicating a slow reaction, represented diagrammatically.

  • Fast Endothermic Reaction:

    • Low E_a leading to a fast reaction.

  • Stepwise Reactions:

    • Multiple energy diagrams are merged for comprehensive understanding, each exhibiting its transition states and energy barriers.

Alkyl Halides

  • Definition:

    • Organic compounds with a halogen atom (X) bonded to an sp3-hybridized carbon.

  • Classification:

    • Primary (1°), Secondary (2°), and Tertiary (3°) based on the number of carbons attached to the halogen-bearing carbon.

  • Types of Alkyl Halides:

    • Vinyl: Halogen on C=C double bond.

    • Aryl: Halogen bonded to benzene ring.

    • Allylic: Halogen on carbon adjacent to a C=C bond.

    • Benzylic: Halogen on carbon adjacent to a benzene ring.

Naming Alkyl Halides

  • Steps for IUPAC Naming:

    • Step 1: Identify the parent carbon chain (alkane).

    • Step 2: Identify the halogen as a substituent attached to the longest chain, applying nomenclature rules (numbering from nearest substituent).

    • Example: For the structure given, 2-chloro-5-methylheptane would be the correct IUPAC name.

  • Common Names: Based on simple alkyl halide naming conventions (alkyl as a single carbon chain with the halogen as a substituent).

Physical Properties of Alkyl Halides

  • Boiling and Melting Points:

    • Alkyl halides have higher boiling/melting points than their corresponding alkanes.

    • Boiling points and melting points increase with larger carbon (R) groups and halogen (X) sizes.

  • Solubility:

    • Alkyl halides are soluble in organic solvents but insoluble in water.

Polarity of Alkyl Halides

  • Alkyl halides display weak polarity due to dipole-dipole interactions from their polar carbon-halogen bonds; cannot engage in hydrogen bonding.

Functional Group Transformations Using Alkyl Halides

  • Nucleophilic Substitutions and Eliminations:

    • Alkyl halides can undergo reactions with nucleophiles (substitution), and bases (elimination), forming new bonds in each scenario.

Factors Affecting Nucleophilicity

  • Definition:

    • Nucleophiles, as Lewis bases, can be negatively charged or neutral with lone pairs or bonds.

  • Key Differences from Bases:

    • Bases attack protons, while nucleophiles attack electron-deficient atoms.

  • Nucleophilicity vs. Basicity:

    • Nucleophilicity is kinetic while basicity is thermodynamic, characterized in reactions with rate constants (k) for nucleophilicity and equilibrium constants (K_a) for basicity.

Steric Effects and Nucleophilicity

  • Concept:

    • Steric hindrance can inhibit nucleophilicity without affecting basicity; sterically hindered bases are poor nucleophiles.

Neutral Nucleophiles and Chemical Reactions

  • Implications:

    • When neutral nucleophiles are involved, the substitution product often bears a positive charge due to proton attachment, leading potentially to loss in subsequent reactions, increasing overall reactivity.

Drawing Reaction Products

  • Nucleophilic Substitution Product Formation:

    • Identify appropriate sp3 hybridized carbon in reactants, locate nucleophile, apply charges as replacements for the leaving group.

Nucleophiles Overview

  • Common Nucleophiles:

    • Negative:   (OH, SH, CN, NH2, etc.)

    • Neutral:   (H2O, ROH, etc.)

  • Solvent Effects:

    • Solvents influence nucleophilicity through solvation; polar protic solvents stabilize ionic intermediates, while polar aprotic solvents enhance reactivity of nucleophiles.

Solvent Impact on Nucleophilicity

  • Solvation in Protic vs. Aprotic Solvents:

    • Protic solvents form strong solvation networks affecting nucleophile reactivity.

    • Aprotic solvents enhance nucleophilicity due to lesser solvation.

Mechanisms of Nucleophilic Substitution

  • SN2 Mechanism:

    • Mechanism characterized by a single-step reaction resulting in inversion of stereochemistry; the rate is dependent on both nucleophile and substrate concentration.

  • Characteristics of SN2:

    • Second-order kinetics, backside attack, yielding inversion at the stereogenic center.

  • SN1 Mechanism:

    • Two-step mechanism where the rate depends solely on the substrate, leading to the formation of carbocation intermediates.

  • Characteristics of SN1:

    • First-order kinetics, producing racemic mixtures due to planar carbocation structures.

Reactivity Trends in Nucleophilic Substitution

  • Factors to Consider in Predictions:

    • Alkyl halide structure influences the prediction of SN1 or SN2 outcomes, analyzed alongside the strength of the nucleophile and solvent type.

  • Carbocation Stability: The reactivity order for carbocations indicates that higher substitution increases carbocation stability favoring SN1 mechanisms.

The Hammond Postulate

  • Definition:

    • Relates reaction rates to transition state stability; asserts that transition states resemble the more stable structure.

  • Implications in Reaction Types:

    • Predicts that in endothermic reactions, transition states align closer to products; in exothermic reactions, they resemble reactants more closely, affecting rate predictions based on stability.

Summary of Factors Influencing SN1 vs. SN2

  • Effect of Leaving Groups and Solvent:

    • Weaker bases serve as superior leaving groups; strong nucleophiles favor SN2 under polar aprotic environments, whereas weak nucleophiles prefer SN1 in polar protic conditions.

Organic Synthesis Overview

  • Definition:

    • The systematic approach to preparing compounds through nucleophilic substitution reactions—central to synthesizing pharmaceuticals and functional compounds.

  • Reverse Thinking:

    • Essential for planning synthesis by determining starting materials and nucleophiles for desired products.