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Chapter 1. Basics of Organic Chemistry

Recommended Post: 【Organic Chemistry】 Organic Chemistry Table of Contents

1. What is Organic Chemistry?

2. Organic Chemistry Structural Formulas

3. Bond Length and Bond Strength

4. Resonance Structures

5. Acid-Base Theory

a. Fundamentals of Chemistry

b. Examples of Physicochemical Properties

1. What is Organic Chemistry?

⑴ Organic Chemistry: The study of compounds primarily composed of carbon.

⑵ The opposite of organic chemistry is inorganic chemistry.

⑶ Currently, about 16 million organic compounds are known.

2. Organic Chemistry Structural Formulas

⑴ Sequence

① SMILES (Simplified Molecular-Input Line Entry System): A short ASCII string representation.

○ Double bonds are represented by ‘=’, and triple bonds are represented by ‘#’.

○ For cyclic compounds, numbers like 1, 2, etc., are assigned to indicate that the ends of a linear molecule are connected to form a ring.

○ Example: CN1C=NC2=C1C(=O)N(C(=O)N2C)C (= caffeine)

○ C represents normal carbon, whereas c represents aromatic carbon

○ C1CCCCC1: cyclohexane

○ c1ccccc1: benzene

○ Brackets can be used to indicate more complex cases.

○ Can also display charge notation like [N+]

○ @ symbol can be used to represent a stereocenter in a molecule.

○ Example: CC@HC@HC

○ / and \ symbols can be used to represent E/Z isomers.

○ Example: CCC/C(=C/C(=O)OCC)/C(=O)OCC

② SMARTS (SMILES arbitrary target specification): Language for specifying structural patterns of molecules.

○ Example: [#6]-[#7]1:[#6]:[#7]:[#6]2:[#6]:1:#6:#7-[#6]

○ Reference: Daylight Chem Info Systems

③ SELFIES (SELF-referencing embedded strings)

○ Example: [C][N][C][=N][C][=C][Ring1][Ring2][C][Branch1_3][epsilon][=O][N][Branch1_3][Branch2_2][C][Branch1_3][epsilon][=O][N][Ring1][Branch1_3][C][C]

○ Reference: NIPS , 2019

④ InChI

○ Example: 1S/C9UBO4/c1-6(10)13-8-S-3-2-4-7(8)9(11)12/h2-5H,1H3,(H,11,12)

○ C9UBO4: Chemical Formula

○ c1-6(10)13-8-S-3-2-4-7(8)9(11)12: Connections of Atoms

○ h2-5H,1H3,(H,11,12): Hydrogen Atoms

⑤ InChIKey

○ Disadvantage of InChI: Can be lengthy

○ InChIKey condenses the InChI into a digital representation using 27 uppercase letters, designed to facilitate web searches.

⑥ Embedding Vector

○ Depending on the type of compression algorithm used, various embedding vectors can exist.

○ Reference: Nature Biotech, 2020

⑵ Basic Structural Formulas

① Kekulé structure (dash formula): Line structural formula without indicating non-bonding electron pairs.

② Lewis structure: Line structural formula indicating non-bonding electron pairs.

③ Lewis dot structure: Lewis structure with shared bond lines represented as electron pairs.

④ Condensed structure

○ Example: CH₃CH₂CH₂CH₃

⑤ Skeletal structure (bond-line formula): Lewis structure without showing carbon and hydrogen atoms.

○ Common in organic chemistry.

○ Carbon atoms often shown to emphasize or clarify.

○ Carbon always forms a tetrahedral structure, so it is assumed that each carbon atom has a corresponding number of hydrogen atoms.

⑶ 3D Structural Formulas: Consideration of stereochemistry.

① Ball-and-stick model

② Space-filling model

Figure 1. Ball-and-stick model and space-filling model

③ Wedge projection (Natta projection): Used for easy consideration of stereochemistry.

○ Wedge lines represent bonds coming out of the plane.

○ Dash lines represent bonds going behind the plane.

○ Solid lines represent bonds in the plane.

○ Tip: RS nomenclature helps determine stereochemistry in wedge projections.

④ Newman projection

○ Projection structure introduced for analyzing conformers.

○ View of single bonds along the bond axis.

○ Nearest carbon to the observer is drawn as a dot, farther carbon as a circle.

○ Hydrogens or substituents attached to each carbon are connected by lines.

⑤ Sawhorse representation

○ Projection structure introduced for analyzing conformers.

○ View of carbon-carbon bonds from an oblique angle.

○ Front carbon shown on the left and inclined downward.

Figure 2. Example of sawhorse representation

⑥ Fisher projection

○ 2D representation of 3D organic molecules invented by Hermann Emil Fischer.

○ Represents stereochemistry with a 2D cross.

○ Represents 3D arrangement in a 2D format using specific rules, instead of wedges and dashes.

○ Rule 1. Horizontal atoms come out of the plane, vertical atoms go into the plane.

○ Rule 2. Only 180° rotations within the plane are allowed.

○ Rule 3. Generally, the most oxidized substituent is placed at the top.

○ In nomenclature, the more oxidized terminal carbon is labeled as 1.

○ Easy to understand by considering the structure of glucose.

Figure 3. Conversion between wedge projection, Newman projection, and Fisher projection

○ Widely used for representing chain-form monosaccharides.

⑦ Haworth projection

○ 3D projection structure used for cyclic monosaccharides.

○ Thick lines indicate positions close to the observer.

○ Unable to distinguish axial and equatorial positions in a cyclic structure.

Figure 4. Haworth projection of glucose

⑷ Organic Chemical Reactions

① →: Reaction arrow

② ⇄: Double reaction arrows (equilibrium arrows)

③ ↔: Double-headed arrow. Resonance structure.

④ ↷: Full-headed curved arrow. Movement of a pair of electrons.

⑤ ⇀: Half-headed curved arrow. Movement of a single electron. Primarily used in radical reactions.

3. Bond Length and Bond Strength

⑴ Bond Strength: Measured by bond dissociation energy.

⑵ Bond Length: Average distance between the nuclei of two atoms participating in a bond.

Figure 5. Average Bond Lengths of Various Bonds (Unit: Å)

⑶ Trends in Bond Strength and Bond Length

①: As bond strength increases, bond length decreases, and vice versa.

② Higher bond order leads to increased bond strength and decreased bond length.

③ Bond length due to hybrid orbitals

○ sp³ - sp³ > sp³ - sp² ＞ sp³ - sp ＞ sp² - sp² ＞ sp² - sp ＞ sp - sp

④ Atomic size: Smaller atomic radius leads to shorter bond length.

⑷ Dipole Moment

4. Resonance Structures

⑴ Overview

① Definition: Delocalization of electrons driven by pi electrons or non-bonding electron pairs.

② Generally, hybrid structures of each atom remain unchanged among resonance contributors.

○ Example: Hybrid orbitals of each oxygen in -COOH are sp2 and p orbitals.

③ Can be divided into resonance involving three or more atoms’ non-bonding electrons and resonance involving non-bonding electrons of two atoms.

④ Electrons move from electron-rich areas to electron-deficient areas.

⑤ Important in benzene acylation mechanism for two atoms’ non-bonding electrons.

⑵ Types of Resonance Structures

① Allylic lone pair, radical, or other double bonds: 2 curved arrows

② Allylic positive charge: 1 curved arrow

③ One pair of electrons near a positive charge: 1 curved arrow

④ Pi bond between two atoms with different electronegativities

⑤ Conjugated pi bonds within a ring structure

Figure 6. Types of Resonance Structures

⑶ Resonance Theory

Figure 7. Resonance Structures of Carbonate Ion

① No single structure accurately represents resonance structures.

② Such individual structures are called resonance or resonance contributors.

③ Real molecules are understood as a mixture of these structures.

② According to X-ray studies, all C-O bond lengths in the carbonate ion are the same; they are longer than double bonds and shorter than single bonds.

⑷ Drawing Resonance Structures

① Resonance structures or contributors are indicated by a double-headed arrow ↔.

○ Chemical equilibrium is indicated by ⇌.

② Resonance structures are formed only by the movement of electrons.

○ 1,2-hydride shift is not a resonance phenomenon.

③ Only pi bond electrons or non-bonding electron pairs can form resonance structures.

④ Total number of electrons within the molecule must remain constant.

⑤ Resonance structures requiring the breaking of sigma bonds are not plausible.

⑥ Second-period elements cannot accommodate more than eight electrons.

⑦ Hydrogen atoms can have only up to two electrons.

⑸ Contribution

① Resonance contribution: Degree to which each structure is favored among resonance contributors.

○ Major contributor: Resonance contributor most similar to the actual structure.

○ Minor contributor: Resonance contributor less similar to the actual structure.

② 1^st. Octet Rule: Resonance contributors violating the octet rule always have the lowest contribution.

○ Example: Resonance contributors with carbocations are likely to be minor contributors.

○ For second-period atoms, no more than 8 electrons in the valence shell.

③ 2^nd. Charge Separation: Resonance contributors without charge separation have higher contributions.

④ 3^rd. Higher electronegativity at the site of a negative charge leads to higher contribution.

⑤ 4^th. If no difference exists among ② ~ ④, resonance contributors with more bonds have higher contributions.

○ Example 1. Zaitsev’s rule

○ Example 2. Electron-donating Inductive Effect

⑹ Examples

① Carbonyl resonance

Figure 8. Carbonyl Resonance

② Oxocarbocation resonance

Figure 9. Oxocarbocation Resonance

③ Allylic system

○ Allylic cation

Figure 10. Allylic Cation Resonance

○ Allyl Anion

Figure 11. Allyl Anion Resonance

④ Nitro Resonance

Figure 12. Nitro Resonance

⑤ Carboxyl System

○ Carboxylic Acid

Figure 13. Carboxylic Acid Resonance

○ Carboxylate Ion

Figure 14. Carboxylate Ion Resonance

⑥ Phenolate Ion

Figure 15. Phenolate Ion Resonance

⑺ Cautions

① Resonance structures of cyclic molecules must consider aromaticity.

○ Cyclic molecules that do not satisfy aromaticity cannot overlap pi bonds between carbons stereoelectronically

○ Example: Cyclooctatetraene does not form resonance structures

Figure 16. Cyclooctatetraene

5. Acid-Base Theory

⑴ All reactions are classified into acid-base reactions (oxidation number change) and redox reactions (oxidation number remains constant).

⑵ General Chemistry: Acid and base theory

⑶ Organic Chemistry: Lewis acid and base

① Lewis acid and base: Thermodynamically, there is a difference between nucleophiles and electrophiles in reaction rates.

○ In organic chemistry, Lewis acids are referred to as electrophiles, and Lewis bases as nucleophiles.

② Nucleophile (Nu): A species that likes nuclei. Reaction-rate related.

○ Example: Electron-rich negative ions, δ^-, carbon-carbon pi bonds.

○ Nucleophilicity can be lower despite strong basicity due to steric hindrance.

○ Basicity: t-butoxide > ethoxide

○ Nucleophilicity: ethoxide > t-butoxide (due to steric hindrance)

③ Electrophile (E): A species that likes electrons. Reaction-rate related.

○ Example: Electron-deficient positive ions, δ+. Mainly on carbon δ+.

○ Reason for Br₂ being an electrophile.

④ Significance of Basicity as a Thermodynamic Concept

○ Thermodynamics is related to the equilibrium state, i.e., the final state.

○ Higher basicity corresponds to lower pK_b with respect to equilibrium constant K_b.

○ That is, basicity indicates which species attracts protons more effectively in the final state.

⑤ Significance of Nucleophilicity as a Reaction Rate Concept

○ Relates to which species reacts more quickly initially.

○ Example: t-BuOK reacts slower than EtOK due to steric hindrance, hence lower nucleophilicity.

⑷ Basicity: The extent of accepting H+. Acidity and basicity are not absolute.

① Overview: Reactivity↑ → Stability ↓ → Basicity ↑

○ Conjugate base of a strong acid is a weak base; conjugate base of a weak acid is a strong base.

○ Acidity and basicity are thermodynamic (reversible reaction exists), while nucleophilicity and electrophilicity are kinetic (irreversible, no reverse reaction).

○ Example: t-BuOK is a strong base but a weak nucleophile.

○ Factors of basicity

○ Factor 1: Inductive Effect: Inductive effect, electronegativity, resonance, hydrogen bonding, size effect.

○ Factor 2: Resonance Effect: Stabilization due to resonance, polarization, backbone bonding, aromaticity effect.

○ Factor 3: Other Effects: Steric hindrance, solvation effect.

○ Introduction of EDG (Electron-Donating Group) and EWG (Electron-Withdrawing Group) concepts considering both inductive and resonance effects.

② 1-1. Inductive Effect: Electron withdrawal or electron donation through σ bonds.

○ Definition: Effect that influences electron density through σ bonds.

○ Differentiate between electron-donating and electron-withdrawing inductive effects.

○ The more functional groups, the more stabilized the carbocation, affecting reaction rate.

Figure 17. Energy levels of carbocations according to substituents

○ Examples:

○ CH₃COOH: The electron-donating effect of the CH₃ group leads to destabilization of the negative charge on the -COO^- group.

○ CF₃COOH: The electron-withdrawing effect of the CF₃ group stabilizes the negative charge on the -COO^- group.

○ CF₃COO^- is more stable than CH₃COO^-, which results in a lower basicity, thus the conjugate acid is stronger.

○ Acidity comparison: CF₃COOH > CH₃COOH

○ Actual pKa values: CF₃COOH pK_a = 0, CH₃COOH pK_a = 5

○ Acidity comparison: (CH₃)₃COH (pK_a = 18) < CH₃CH₂OH (pK_a = 16) < H₂O (pK_a = 15.7)

③ 1-2. Electronegativity: Increases with increasing group number, leading to increased stability and decreased basicity.

○ For elements in the same period, having negative charge on atoms with greater electronegativity results in stability, while having positive charge on such atoms results in instability.

○ Basicity: F^- < OH^- < NH₂^- < CH₃^- (due to electronegativity)

○ Acidity: HF (pK_a = 3.2) > H₂O (pK_a = 15.7) > NH₃ (pK_a = 38) > CH₄ (pK_a = 50)

④ 1-3. Mixed Effect: As s-character increases, acidity increases

○ Hyperconjugation

○ Definition: The phenomenon where sigma bonding provides electrons to anti pi bonding, stabilizing the compound.

○ In the order of sp ＞ sp² ＞ sp³, electronegativity is stronger, so sp³ carbon provides electrons to sp and sp² carbon.

○ Reason: In the order of sp ＞ sp² ＞ sp³, the spheric orbital, which is s character, is stronger, bringing it closer to the nucleus → increase in electronegativity.

○ sp Hybridization: Among 2 hybrid orbitals, 1 s orbital → 50 % s-character

○ sp² Hybridization: Among 3 hybrid orbitals, 1 s orbital → 33 % s-character

○ sp³ Hybridization: Among 4 hybrid orbitals, 1 s orbital → 25 % s-character

○ Example 1.

○ Basicity: CH₃CH₂^- > C₂H₃^- > C₂H^-

○ Acidity: CH₃CH₃ (pK_a = ~50) < C₂H₄ (pK_a = 44) < C₂H₂ (pK_a = 25)

○ Example 2. Basicity: pyridine < piperidine

Figure 18. pyridine(top) and piperidine(bottom)

○ The N in pyridine is sp² and in piperidine is sp³, so H⁺ is more likely to approach piperidine with smaller s-character.

○ The resonance stabilization in pyridine exists before and after the acid-base reaction, thus it is canceled out.

○ Basicity: alkyl amine (sp³) > pyridine (participating in resonance) > aniline (participating in resonance) > pyrrole (participating in resonance) > amide (participating in resonance)

○ Example 3. Comparison of piperidinium and aziridinium

○ Example 4. Influence of acidity by remote hybridization

○ propyl alcohol (pK_a: 16.1), prop-2-en-1-ol (pK_a: 15.5), benzenemethanol (pK_a: 15.4), prop-2-yn-1-ol (pK_a: 13.5) 

○ propanoic acid (pK_a: 4.9), prop-2-enoic acid (pK_a: 4.2), benzenemethanoic acid (pK_a: 4.2), prop-2-ynoic acid (pK_a: 1.9)

⑤ 1-4. Hydrogen Bonding: Acidity increases when conjugate bases can form intramolecular hydrogen bonds.

○ Example: o-aminophenol is more acidic than p-aminophenol.

Figure 19. Stabilization of o-aminophenol’s conjugate base through hydrogen bonding

○ Strong intramolecular hydrogen bonding leads to weaker intermolecular hydrogen bonding.

⑥ 1-5. Size Effect

○ Larger polarization (∝ size) leads to better nucleophilicity, making overlap with σ* easier in the transition state.

○ Opposite to 2-2 explanation

○ Example 1. Nucleophilicity: H₂O ＜ H₂S ＜ H₂Se

○ Example 2. Nucleophilicity: NH₃ ＜ PH₃

⑦ 2-1. Resonance Stabilization Effect: Resonance structures increase stability, reducing basicity.

○ Multiple resonance contributors lead to energetic stability.

○ Particle in a box: Electron delocalization decreases energy (∝ 1 / L²).

○ Example: Carboxylic acid anion is stable and harmless due to resonance.

○ Basicity: CH₃CH₂O^- > CH₃COO^- (due to resonance stabilization)

○ Acidity: CH₃CH₂OH (pK_a = 16) < CH₃COOH (pK_a = 5)

⑧ 2-2. Polarization: More electron shells lead to reduced electron-electron repulsion, increasing stability and reducing basicity.

○ Applicable mainly to HX compounds.

○ Basicity: F^- > Cl^- > Br^-

○ Acidity: HF (pK_a = 3.2) < HCl (pK_a = -7) < HBr (pK_a = -9)

⑨ 2-3. Backbonding: p orbital electrons interact with vacant d orbitals, stabilizing the molecule.

○ Example: Comparison of CHF₃ and CHCl₃

○ Acidity: CHF₃ < CHCl₃

○ Conjugate base stability: CF₃^- < CCl₃^-

○ Interpretation: Cl has 3d orbitals where electrons can be placed, thus excess electrons from carbon’s 2p orbital can be stabilized by delocalizing in Cl’s 3d orbitals.

○ Electron-withdrawing inductive effect is stronger in CF₃^- than CCl₃^-, which can be misleading about the stability of conjugate bases.

○ Remember the trend of acidity: HF < HCl < HBr < HI, which makes understanding backbonding easier.

⑩ 2-4. Aromaticity Effect

○ A type of resonance stabilization effect.

○ If the conjugate base possesses aromaticity, the special stabilization due to resonance leads to higher acidity.

○ If the conjugate base is anti-aromatic, it’s highly unstable, resulting in lower acidity.

⑪ 3-1. Steric Hindrance

○ Acidity: Ethanol (pK_a = 16) > t-butanol (pK_a = 18)

○ Basicity: ethoxide < t-buthoxide

○ If nucleophile is large, t-butoxide’s steric hindrance can overcome its stabilization in solvent, leading to stronger nucleophilicity of ethoxide.

⑫ 3-2. Solvation Effect

○ Definition: The phenomenon where a separated conjugate base is stabilized by the surrounding solvent.

○ Note: Basicity is not affected, only nucleophilicity is affected.

○ Dielectric constant: Higher dielectric constants indicate stronger polarity, enhancing solvation effect.

○ Polar protic solvents (e.g., water) have higher dielectric constants compared to polar aprotic solvents (e.g., DMSO, DMF).

○ Positive protic solvents: Easier stabilization with smaller-size electronegative atoms. Larger atoms have less electron density, leading to weaker ion-solvent interaction.

○ Basicity: I^- < Br^- < Cl^- < F^-

○ Nucleophilicity: I^- > Br^- > Cl^- > F^-

○ Basicity: SeH^- < SH^- < OH^-

○ Nucleophilicity: SeH^- > SH^- > OH^-

○ Basicity: tert-butoxide > ethoxide (due to steric hindrance)

○ I^- is a good leaving group and nucleophile in water.

○ For elements in the same period, electronegativity dictates the trend. CH₃^- > H₂N^- > HO^- > F^-

○ Nonpolar aprotic solvents: Nucleophilicity follows the trend of basicity due to lack of intramolecular hydrogen bonding.

○ Basicity: I^- < Br^- < Cl^- < F^-

○ Nucleophilicity: I^- < Br^- < Cl^- < F^-

○ Basicity: SeH^- < SH^- < OH^-

○ Nucleophilicity: SeH^- < SH^- < OH^-

○ I^- shows increased basicity in protic solvents compared to nonpolar aprotic solvents.

○ Solvent hydrogen bonding increases basicity but reduces stability.

⑸ pK_a values to memorize in organic chemistry

① Lower pK_a means stronger acid, lower pK_b means stronger base.

② The listed pK_a values are measured in water and may differ in DMSO or other solvents.

Table 1. Essential Memorization of pK_a

Input: 2019.01.08 23:05