Organizing Organic Chemistry E-Book

Jeongbin Park

• Herausgeber: 이즈그리민(izgrimean)
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 116

Veröffentlichungsjahr: 2024

Beschreibung

The "Laboratory Reactions" edition describes organic reactions that occur under strong reaction conditions, offering fundamental concepts of organic chemistry. It serves as an essential guide for students and professionals in organic chemistry, providing a comprehensive overview of both fundamental and advanced organic reactions. Designed to facilitate learning and practical application, this book bridges the gap between theoretical concepts and real-world practice.

In "Laboratory Reactions," readers will find a well-structured and detailed exploration of organic reactions, starting with basic principles and progressing to more complex topics. Each chapter is carefully written to make complex concepts easy to understand with the help of illustrative examples, often with YouTube clips, and useful chemoinformatics applications with Python codes.

I opened a blog called “Jeongbin’s Study Room” to collect knowledge from many people. The enthusiasm for organic chemistry is still strong today, but a few years ago, it was significant, as organic chemistry was essential for various exams. Since studying organic chemistry in elementary, middle, and high school was rare, I anticipated a significant academic demand for organic chemistry. Therefore, since 2018, I have been sharing articles on organic chemistry on “Jeongbin’s Study Room” and communicating, correcting, and discussing with people. I have had many discussions online with medical professionals, pharmacists, lawyers, current teachers, and professors, among others. Now, as we welcome the new year 2024, I declare that the compilation of organic chemistry knowledge through collective intelligence is complete and I am publishing this book. I hope that this book can lower the barrier of organic chemistry as a field of study.

Leseprobe

Creative Commons

Organizing Organic Chemistry

Laboratory Reactions

Author | Jeongbin Park

Editor | Jeongbin Park

Cover Design | EUNJOLEE

Published by | 이즈그리민(izgrimean)

Publisher | EUNJOLEE

Date of Publication | June 19, 2024

Publisher Registration | May 24, 2023, No. 2023-000052

Email | [email protected]

First Edition eBook Published | June 19, 2024

Price |

ISBN | 979-11-987080-4-5(95430)

© 2024, 이즈그리민(izgrimean). All rights reserved. Reproduction or distribution of this work, in whole or in part, without explicit permission from 이즈그리민(izgrimean) is prohibited by law.

For reuse of any part of this book, permission must be obtained from both the copyright holder and 이즈그리민(izgrimean).

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Getting Started

Comments from Jeongbin Park

I opened a blog called “Jeongbin’s Study Room” to collect knowledge from many people. The enthusiasm for organic chemistry is still strong today, but a few years ago, it was significant, as organic chemistry was essential for various exams. Since studying organic chemistry in elementary, middle, and high school was rare, I anticipated a significant academic demand for organic chemistry. Therefore, since 2018, I have been sharing articles on organic chemistry on “Jeongbin’s Study Room” and communicating, correcting, and discussing with people. I have had many discussions online with medical professionals, pharmacists, lawyers, current teachers, and professors, among others. Now, as we welcome the new year 2024, I declare that the compilation of organic chemistry knowledge through collective intelligence is complete and I am publishing this book. I hope that this book can lower the barrier of organic chemistry as a field of study.

If you send the purchase receipt of the book to [email protected], we will provide you with additional lecture materials and problem sets.

Ch. 1: Organic Reaction Overview

Ch. 1: Organic Reaction Overview

1. Overview

2. Types of Organic Reactions

3. Reaction Thermodynamics and Reaction Kinetics

4. Reaction Mechanism

5. Energy Diagram

1. Overview

⑴ Reaction : The phenomenon where the bonds of the reactants break and the bonds of the products form.

⑵ Reaction equation

① Types of arrows

○ → : Reaction arrow

○ ⇄ : Double reaction arrows. Indicates chemical equilibrium.

○ ↔ : Double-headed arrow. Indicates resonance structures.

○ ↷ : Full-headed curved arrow. Indicates movement of a pair of electrons.

○ ⇀ : Half-headed curved arrow. Indicates movement of a single electron.

② Reagents are indicated on the left side of the reaction equation or above the arrow.

③ Solvents and temperature in the reaction are indicated above or below the arrow.

④ In multistep reactions, reagents are denoted as [1], [2], and so on.

⑶ All reactions can be categorized as acid-base reactions and redox reactions, but can be further classified based on mechanisms.

① Acid-base reactions specified separately in mechanisms refer to general acid-base reactions with terminal functional groups, and they are fastest.

⑷ Intramolecular reactions are much faster than intermolecular reactions.

① Many quizzes in organic chemistry focus on intramolecular reactions.

② When conditions allow intramolecular SN2 reactions, these reactions should proceed because intramolecular reactions are significantly faster.

③ If conditions allow ring-closure reactions (e.g., epoxidation), there reactions should proceed.

2. Types of Organic Reactions

⑴ Substitution reaction

Figure 1. Example of substitution reaction

⑵ Elimination reaction

Figure 2. Example of elimination reaction

⑶ Addition reaction

Figure 3. Example of addition reaction

3. Reaction Thermodynamics and Reaction Kinetics

⑴ Reaction Thermodynamics: Related to ΔG°.

① Entropy

○ Reaction with more products than reactants increases entropy, and reaction with fewer products decreases entropy.

○ Linear molecules becoming cyclic reduce degrees of freedom, hence decrease in entropy.

② Free energy

○ This concept is not applicable to gas-phase reactions, hence entropy values related to it are generally low.

○ In organic reactions that don't proceed at high temperatures, the effect of entropy term is small, making the changes in free energy and enthalpy nearly identical.

○ Organic chemistry deals only with spontaneous reactions anyway, so the concept of free energy isn't crucial.

① Important in organic chemistry.

② Activation energy

○ Most organic reactions have activation energy of 40 to 150 kJ/mol.

○ Reactions with activation energy below 80 kJ/mol proceed easily at room temperature.

③ Catalyst: Reduces activation energy, thereby increasing reaction rate.

⑶ Natural noise in the environment: 80 kJ/mol

① Energy involved in conformational changes (ringflip) is generally less than 80 kJ/mol.

② Energy involved in organic reaction is much larger than this noise.

⑷ Hammond Postulate

① Introduction

○ Reaction rate is dependent on the energy of the transition state.

○ As the precise configuration of the transition state remains unknown, its arrangement is deduced from either the reactants or the products.

② Explanation

○ Transition state resembles energetically similar chemical species.

○ Transition state for endothermic reactions resembles products, while that for exothermic reactions resembles reactants.

○ Reactions that produce intermediates are typically endothermic. If the intermediate is a stable compound, it is assumed that the transition state leading to the intermediate would also be stable and resemble the intermediate. Therefore, in such cases, the reaction can proceed easily to form the final product.

⑸ Hoffmann's Law : It derives concepts of rate control and thermodynamic control.

① Experiment

Figure 4. The addition of hydrogen halides to 1,3-butadiene

○ 0 °C: 3-bromobut-1-ene (71%) + 1-bromobut-2-ene (29%)

○ 40 °C: 3-bromobut-1-ene (15%) + 1-bromobut-2-ene (85%)

② Interpretation

○ 1,2 addition : Formation of 3-bromobut-1-ene.

○ 1,4 addition : Formation of 1-bromobut-2-ene.

○ According to the mechanism, generation of 3-bromobut-1-ene is more reasonable.

○ At high temperatures, reverse reaction occurs, hence thermodynamically more stable product dominates.

○ 0 °C (low temperature): Product ratio is determined by rate control.

○ 40 °C (high temperature): Product ratio is determined by thermodynamic control.

4. Reaction Mechanism

⑴ Transition State Theory : Reactions occur via transition states.

① Transition state: Most unstable state during reaction.

② Reasons for instability of transition state: Violation of octet rule, charge separation, etc.

③ Activation energy: Energy difference between transition state and reactants.

④ Among various possible transition states, reaction proceeds along the path with the lowest activation energy.

⑵ Categorization of reactions based on mechanism steps

① One-step reaction

○ Also known as concerted reaction.

○ Breaking of reactant bonds and forming of product bonds occur simultaneously.

○ Reaction rate analysis: Reaction rate is proportional to the product of reactant concentrations.

② Stepwise reaction

○ Reaction proceeds via unstable intermediates.

○ Mechanism: Reactant → Transition state → Intermediate → Transition state → Product

○ Reaction rate analysis: Rate-determining step exists; generally, reaction rate is proportional to the concentration of one reactant.

⑶ Categorization of reactions based on mechanism types

① Homolysis (homolytic cleavage): Homolytic cleavage occurs in radical reactions, symmetrical bonds, and C-H bonds.

Figure 5. Homolysis

② Heterolysis (heterolytic cleavage): Heterolytic cleavage occurs due to polar reactions, differences in electronegativity, differences in polarity, etc.

○ Example: Most organic chemistry reactions, Cl-Cl reactions, Br-Br reactions, cases with double bonds

Figure 6. Heterolysis

③ Energy is required for bond cleavage.

⑷ Types of intermediates

① Radical

Figure 7. Radical

○ Intermediate with unpaired electron.

○ Formed through homolysis reactions.

○ Highly unstable as it does not follow the octet rule.

○ Generally, does not possess charge.

○ sp2 hybridization.

② Carbocation: Violates octet rule, so it is unstable. Trigonal planar.

Figure 8. Carbocation

○ Reaction creating carbocation has the carbocation formation step as the rate-determining step.

○ Carbocation allows rearrangement.

○ Carbocation can undergo racemization.

○ Electron-donating inductive effect: More alkyl groups around carbocation (up to 3 maximum) stabilize carbocation itself.

○ Alkyl groups (C) have electronegativity of 2.5, while hydrogen (H) has electronegativity of 2.1, showing different tendencies than electronegativity.

○ Hydrogen has only one electron, hence showing a different tendency than electronegativity.

○ It is also related to the hyperconjugation discussed below.

○ Stability order

○ Benzyl carbocation ≈ Allyl carbocation ≈ Tertiary carbocation > Secondary carbocation > Primary carbocation > Methyl carbocation > Vinyl carbocation

Figure 9. The stability of carbocation according to the electron-donating inductive effect

○ Tertiary allylic cation ＞ Secondary allylic cation ＞ Allyl cation

○ Tertiary benzylic cation ＞ Secondary benzylic cation ＞ Benzyl cation

○ Hyperconjugation

Figure 10. Hyperconjugation

○ Definition : Weak delocalization of alkyl group's sp3 orbital electron onto the empty p orbital of carbocation.

○ sp3 bonding acts like a sigma bond, but behaves like a pi bond, causing electron delocalization.

○ Hydrogen's s orbital cannot delocalize onto carbocation's empty p orbital.

○ Stability assessment : More alkyl groups around carbocation lead to stabilization.

○ Cause of rearrangement reaction

○ Hyperconjugation weakens nearby carbon's C-H bond (Type 1) or C-Me bond (Type 2).

○ Type 1. 1,2-hydride shift

Figure 11. 1,2-hydride shift

○ Type 2. 1,2-methyl shift

Figure 12. 1,2-methyl shift

○ sp2 carbocation is more stable than sp carbocation : sp carbocation has higher s-character, hence nucleus's influence is stronger.

③ Carbanion : Satisfies octet rule, but carbon with low electronegativity bears negative charge, causing instability.

Figure 13. Carbanion

5. Energy Diagram

⑴ Bond dissociation energy

① Definition: Energy required to break covalent bonds. It is generally positive.

② Bond strength: Higher bond strength → Greater stability → Higher bond dissociation energy.

③ Enthalpy change and bond dissociation energy

④ Bond dissociation energy is measured for reactions in the gaseous state, hence only approximated values are provided for organic reactions.

⑵ Energy diagram

① x-axis represents reaction coordinate, and y-axis represents energy.

② One-step reaction: Single transition state

③ Multistep reaction: Multiple transition states. Intermediates exist.

④ Activation energy: Energy difference between transition state and reactant (if no intermediate) or intermediate (if any).

⑤ Rate-determining step of multistep reactions: Reaction rate of the step with the highest activation energy.

Ch. 2: Organic Reaction Commons

Ch. 2: Organic Reaction Commons

1. Names of Carbon

2. Acid and Base

3. Nucleophiles

4. Leaving Groups

5. Solvent

6. EDG, EWG

1. Names of Carbon

⑴ Names of Hydrogens and Carbons Depending on Functional Group Position

Figure 1. Names of Hydrogens and Carbons Depending on Functional Group Position

① α carbon: Carbon directly attached to the functional group (e.g., X-).

② α hydrogen: Hydrogen attached to the α carbon.

③ β carbon: Carbon adjacent to the α carbon.

④ β hydrogen: Hydrogen attached to the β carbon.

⑵ Carbon's Degree

① Primary Carbon: Carbon with only one neighboring carbon bonded to it.

② Secondary Carbon: Carbon with two neighboring carbons bonded to it.

③ Tertiary Carbon: Carbon with three neighboring carbons bonded to it.

④ Quaternary Carbon: Carbon with four neighboring carbons bonded to it.

⑤ Applications: n-degree alcohols, n-degree alkyl halides, n-degree amines.

⑶ Carbon's Position

① Vinyl Carbon: Carbon with a double bond.

② Allyl Carbon: Carbon next to a vinyl carbon.

③ Benzyl Carbon: Carbon next to a phenyl group (i.e., benzene functional group).

2. Acid and Base

⑴ Thermodynamic Concepts.

⑵ Strong Acids

① Major pKa values to memorize in organic chemistry

② TsOH > HI > HBr > HCl > HF

③ CF3SO3H (superacid): A very strong acid that protonates key functional groups to facilitate subsequent reactions.

○ Main functional groups that accept H+: olefins (i.e., alkenes), alcohols, ethers, carbonyl compounds, amines, etc.

○ Donates H+ to all of these functional groups.

○ Creates strong electrophiles that react with less reactive aromatic compounds: superacid-catalyzed Friedel-Crafts reaction.

○ Can even induce reactions that disrupt aromaticity.

Figure 2. Reaction of superacid breaking aromaticity.

⑶ Strong Bases

① NaOEt, NaOMe

② NaNH2: Involved in E2 reaction.

③ t-BuOK

④ CN-

⑤ n-BuLi

⑥ KOCEt3

⑦ LDA(lithium diisopropylamide)

⑷ Weak Acids

① EtOH

② BF3

③ FeCl3

⑸ Weak Bases

① NaHCO3

3. Nucleophiles:

⑴ Reaction Kinetics Concepts.

⑵ Comparison of Nucleophilicities of Ions with the Same Group but Different Periods: Larger period implies stronger nucleophilicity.

① Example: CH3O- < CH3S-

⑶ Comparison of Nucleophilicities of Neutral Nucleophiles: Larger atoms have greater polarizability, leading to stronger nucleophilicity.

① Strong Nucleophiles: RMgX, R2CuLi, NaNH2, NaOR, KC≡CH

② Weak Nucleophiles: t-BuOK, NaCN, KN3, RNH2, RCOONa, NaSR, NaBR, KI

○ t-BuOK is a strong base but a weak nucleophile due to steric hindrance.

③ Strong Nucleophiles

④ Weak Nucleophiles

4. Leaving Groups

⑴ Leaving ability increases with leaving group stability.

⑵ Major Leaving Groups Comparison

① TfO- > TsO- > MsO- > I- > Br- > Cl- > H2O ≫ F- > OH- > OR- > NH2-

② H2O is a major leaving group in alcohol reactions.

③ Halogens: Leaving ability is inversely related to basicity.

⑶ Comparison of Solvation Reaction Rates of 1-Phenylethyl Sulfonate Esters Depending on Leaving Group Type

① CF3SO3-: 1.4 × 108

② p-Nitrobenzenesulfonate: 4.4 × 105

③ p-Toluenesulfonate: 3.7 × 104

④ CH3SO3-: 3.0 × 104

5. Solvents

⑴ Criteria for Solvents

① Should dissolve reactants.

○ Acid-base reactions should not be conducted in nonpolar solvents.

② Should not participate in the reaction.

○ Toluene solvent shouldn't be used in halogen addition reactions since it participates in the reactions.

○ Solvent for making Grignard reagents should not be acidic: In this case, anhydrous ether is often used.

③ It should have a low boiling point in order to evaporate later and separate the product.

④ Polar aprotic solvents needed for SN2 reactions.

⑤ Organic solvents with higher density than water needed in certain cases.

○ Organic solvents with higher density than water: CS2, CCl4, CHCl3, CH2Cl2, CH3Cl, DMSO

○ Purpose 1. These solvents are used in conjunction with a separatory funnel.

⑵ Class 1. Polar Protic Solvents (PPS): Solvents with hydrogen bonding.

① Ionizing nucleophiles are less nucleophilic in these solvents.

② Example: Water (H2O), Ethanol (EtOH), Methanol (MeOH)

③ SN2: Nucleophile's charge is stabilized by solvent's hydrogen ion, reducing reaction rate.

⑶ Class 2.