Organic Chemistry Finals Review - Comprehensive Guide

Part I: The Foundation - Structure, Bonding, and Molecular Architecture

Key Principle: The architecture of a molecule—how its atoms are bonded and arranged in three-dimensional space—dictates its physical properties and chemical reactivity.

1.1: The Language of Organic Chemistry: Atoms, Electrons, and Bonds

Atomic Structure Fundamentals

Organic chemistry's vast diversity originates from the unique bonding properties of key elements, primarily carbon. Understanding atomic structure is crucial:

Atomic Number (Z): Defines an element by its number of protons
Mass Number (A): Sum of protons and neutrons
Valence Electrons: Outermost electrons that participate in chemical bonding

Tip: The configuration of valence electrons determines an atom's bonding capacity and behavior.

The Octet Rule

The primary driving force for bond formation is the completion of the valence shell to achieve a stable configuration of eight electrons (like noble gases).

Examples:
• Carbon (2s²2p²): Forms 4 covalent bonds
• Nitrogen (5 valence e⁻): Forms 3 bonds + 1 lone pair
• Oxygen (6 valence e⁻): Forms 2 bonds + 2 lone pairs

Important: Violations of the octet rule often indicate highly reactive, unstable species such as carbocations, which are key intermediates in many reactions.

Lewis Structures and Covalent Bonding

Lewis structures represent valence electrons as dots. A covalent bond consists of a pair of shared electrons between two atoms.

Methane (CH₄): C shares one electron with each of four H atoms
H
|
H-C-H
|
H

1.2: The Geometry of Carbon: Hybridization

Key Concept: Hybridization is the mathematical mixing of an atom's native atomic orbitals (s and p) to generate new hybrid orbitals with correct geometry for maximum stability.

Types of Hybridization

Hybridization	Geometry	Bond Angles	Example	Bond Types
sp³	Tetrahedral	109.5°	Methane (CH₄), Ethane	All σ bonds
sp²	Trigonal Planar	120°	Ethylene (C₂H₄)	σ + π bonds
sp	Linear	180°	Acetylene (C₂H₂)	σ + 2π bonds

sp² Hybridization Details: In ethylene, the unhybridized p orbital is perpendicular to the molecular plane. The π bond forms from side-by-side overlap of p orbitals, creating electron density above and below the molecular plane - making it a nucleophilic site susceptible to electrophilic attack.

1.3: Functional Groups - The Cast of Characters

Master Principle: A functional group is a specific collection of atoms that exhibits characteristic and predictable reactivity, largely independent of the molecule's carbon framework.

Functional Group	Structure	Name Ending	Example
Multiple C-C Bonds
Alkene (double bond)	C=C	-ene	H₂C=CH₂ (Ethene)
Alkyne (triple bond)	−C≡C−	-yne	HC≡CH (Ethyne)
Arene (aromatic)	Benzene Ring	None	Benzene
With Electronegative Atoms
Halide	−C−X (X=F,Cl,Br,I)	None	CH₃Cl (Chloromethane)
Alcohol	−C−OH	-ol	CH₃OH (Methanol)
Ether	−C−O−C−	ether	CH₃OCH₃ (Dimethyl ether)
Amine	−C−N	-amine	CH₃NH₂ (Methylamine)
Thiol	−C−SH	-thiol	CH₃SH (Methanethiol)
Sulfide	−C−S−C−	sulfide	CH₃SCH₃ (Dimethyl sulfide)
Carbonyl-Containing Groups
Aldehyde	−CHO	-al	CH₃CHO (Ethanal)
Ketone	−C(O)−	-one	CH₃C(O)CH₃ (Propanone)
Carboxylic Acid	−COOH	-oic acid	CH₃COOH (Ethanoic acid)
Ester	−COOR	-oate	CH₃COOCH₃ (Methyl ethanoate)
Amide	−CONH₂	-amide	CH₃CONH₂ (Ethanamide)

Part II: Isomerism and Three-Dimensional Structure

2.1: IUPAC Nomenclature - Naming the Molecules

IUPAC Grammar: Locant-Prefix-Parent-Suffix

Nomenclature Components

Parent: Longest continuous chain of carbon atoms
Suffix: Identifies the primary functional group (-ane, -ol, etc.)
Prefix: Identifies substituents attached to parent chain
Locant: Number indicating position of substituent/functional group

Systematic Naming Process

Step 1: Find the Parent Chain/Ring - Identify longest continuous carbon chain (acyclic) or compare ring vs. largest substituent (cyclic)

Step 2: Number the Parent - Start from end giving first substituent lowest number; for ties, give second substituent lowest number

Step 3: Name and Alphabetize Substituents - Name as alkyl groups, list alphabetically (ignore di-, tri- prefixes)

Example: 4-Ethyl-3-methylheptane
Numbering from right: substituents at positions 3,4
Numbering from left: substituents at positions 4,5
Since (3,4) < (4,5), number from right is correct

2.2: Conformational Analysis - The Shapes of Alkanes and Cycloalkanes

Key Concept: Rotation around single (σ) bonds is rapid at room temperature, leading to different three-dimensional arrangements called conformations.

Acyclic Systems: Butane Conformations

Newman projections view molecules along C-C bonds to analyze conformational energy:

Conformation	Energy	Description	Strain Type
Anti	Lowest	Methyl groups 180° apart	Minimal strain
Gauche	Intermediate	Methyl groups 60° apart	Steric strain
Eclipsed	Highest	Groups directly aligned	Steric + Torsional strain

Cyclic Systems: Cyclohexane Chair Conformations

Cyclohexane adopts a chair conformation that is completely free of angle and torsional strain.

Two Types of Positions:
• Axial: Perpendicular to ring plane (pointing up/down)
• Equatorial: Point out from ring "equator"

Ring-Flip Process: Chair conformations rapidly interconvert - all axial positions become equatorial, and vice versa.

1,3-Diaxial Interactions: Axial substituents experience destabilizing interactions with other axial hydrogens. For methyl groups, this penalty is 7.6 kJ/mol, equivalent to two gauche-butane interactions (2 × 3.8 kJ/mol).

2.3: Stereochemistry - Chirality and Optical Activity

Definition: Stereoisomers have the same molecular formula and connectivity but different three-dimensional arrangements.

Chirality Fundamentals

A chiral object is not superimposable on its mirror image. Molecules are chiral if they lack a plane of symmetry.

Most Common Cause: Presence of a chirality center - a carbon bonded to four different groups.

Stereoisomer Type	Relationship	Properties
Enantiomers	Non-superimposable mirror images	Identical physical properties except optical rotation
Diastereomers	Stereoisomers that are NOT mirror images	Different physical properties

R/S Configuration Assignment (Cahn-Ingold-Prelog System)

Step 1: Assign priorities to four groups based on atomic number (higher = higher priority)

Step 2: Orient molecule so lowest priority group points away from viewer

Step 3: Trace path from highest → second highest → third highest priority

Step 4: Clockwise = R (rectus), Counterclockwise = S (sinister)

Meso Compounds

Molecules with multiple chirality centers but overall achiral due to internal plane of symmetry. Example: tartaric acid.

Biological Significance: Enzymes and receptors can distinguish between enantiomers due to their chiral nature. One enantiomer may be therapeutic while its mirror image could be inactive or toxic (e.g., thalidomide).

Part III: The Heart of Reactivity - Alkenes and Their Reactions

3.1: Electrophilic Addition - The Core Mechanism

Fundamental Principle: The electron-rich π bond acts as a nucleophile and attacks electrophiles in a characteristic two-step mechanism.

General Mechanism

Step 1 (Slow, Rate-Determining): Alkene π bond attacks electrophile (e.g., H in HBr), forming new C-H bond and carbocation intermediate

Step 2 (Fast): Nucleophile (e.g., Br⁻) rapidly attacks carbocation to form final product

Markovnikov's Rule and Carbocation Stability

When adding unsymmetrical reagents to unsymmetrical alkenes, the hydrogen adds to the carbon that already has more hydrogens.

Carbocation Stability Order:
Tertiary (3°) > Secondary (2°) > Primary (1°) > Methyl
Due to stabilizing effects of alkyl groups

Hammond Postulate: The transition state of an energy-uphill step resembles the product. Factors stabilizing carbocations also stabilize transition states, lowering activation energy.

Carbocation Rearrangements

Less stable carbocations can rearrange via 1,2-hydride or 1,2-alkyl shifts to form more stable ones before nucleophile attack.

Exam Alert: Carbocation rearrangements are common sources of unexpected products and frequent exam topics.

3.2: Survey of Key Addition Reactions

Reaction	Reagents	Mechanism	Stereochemistry	Rearrangement?
Halogenation	Br₂, Cl₂	Bridged halonium ion	Anti-addition	No
Halohydrin Formation	Br₂/H₂O	Bridged halonium ion	Anti-addition	No
Acid-Catalyzed Hydration	H₂O/H⁺	Carbocation	No stereocontrol	Yes
Oxymercuration-Demercuration	Hg(OAc)₂/H₂O, NaBH₄	Bridged mercurinium ion	Anti-addition	No

Halogenation Details

Addition of Br₂ or Cl₂ proceeds through a three-membered, bridged bromonium ion intermediate.

Key Features:
• Nucleophile attacks from face opposite the halogen bridge
• Results in stereospecific anti-addition
• No carbocation rearrangements occur

Oxymercuration-Demercuration Advantages

Superior Method: Provides clean Markovnikov addition of water without carbocation rearrangements due to bridged mercurinium ion intermediate.

3.3: Oxidation and Reduction of Alkenes

Catalytic Hydrogenation (Reduction)

Addition of H₂ across double bond using metal catalysts (Pt, Pd, Ni).

Mechanism: Both hydrogen atoms delivered to same face of alkene on metal surface
Result: Syn-addition

Ozonolysis (Oxidative Cleavage)

Powerful reaction that completely cleaves the double bond using ozone (O₃).

Process:
1. Alkene + O₃ → unstable intermediate
2. Workup (Zn/H₂O) → two carbonyl fragments (aldehydes/ketones)

Retrosynthetic Application: Given cleavage products, deduce original alkene structure by reconnecting carbonyl carbons to reform double bond.

Part IV: Competing Pathways - Substitution vs. Elimination

Challenge: Four distinct mechanisms (SN1, SN2, E1, E2) compete constantly. Success requires systematic analysis of reaction conditions.

4.1: Nucleophilic Substitution Reactions

Mechanism	Steps	Kinetics	Stereochemistry	Substrate Preference
SN2	Concerted (1 step)	Bimolecular	Inversion (Walden)	Methyl, 1° > 2° >> 3°
SN1	Two-step via carbocation	Unimolecular	Racemization	3° > 2° >> 1°

SN2 Mechanism Details

Process: Nucleophile attacks carbon from side opposite leaving group (backside attack)

Result: Complete inversion of stereochemistry at chiral center

Sensitivity: Highly sensitive to steric hindrance

SN1 Mechanism Details

Step 1 (Slow): Leaving group departs, forming planar carbocation

Step 2 (Fast): Nucleophile attacks carbocation from either face

Result: Racemization or partial inversion

4.2: Elimination Reactions

Mechanism	Steps	Base Requirement	Geometric Requirement	Product Selectivity
E2	Concerted (1 step)	Strong base	Anti-periplanar	Zaitsev's Rule
E1	Two-step via carbocation	Weak base (typically)	None	Zaitsev's Rule

E2 Mechanism Critical Features

Anti-Periplanar Requirement: The proton being removed and leaving group must be trans and in the same plane for efficient orbital overlap.

Process: Base removes proton while leaving group departs simultaneously

Result: Highly stereospecific reaction

Zaitsev's Rule

Both E1 and E2 reactions generally favor formation of the more substituted (more stable) alkene.

Alkene Stability Order:
Tetrasubstituted > Trisubstituted > Disubstituted > Monosubstituted

4.3: The Unified Framework - Predicting Outcomes

Key Insight: View the four pathways as being in competition rather than simple on/off switches. Conditions tilt the energetic balance toward one major product.

Four Critical Factors for Analysis

1. The Substrate (Most Important):
• Methyl, 1°: Strongly favor SN2
• 3°: Cannot undergo SN2; favor SN1/E1 (weak bases) or E2 (strong bases)
• 2°: The battleground - all four mechanisms possible

2. The Reagent:
• Strong bases (HO⁻, RO⁻): favor E2
• Strong nucleophiles/weak bases (I⁻, RS⁻): favor SN2
• Weak bases/nucleophiles (H₂O, ROH): favor SN1/E1

3. The Leaving Group:
Good leaving groups (conjugate bases of strong acids): I⁻, Br⁻, Cl⁻, TsO⁻
Poor leaving groups (OH⁻) require protonation first

4. The Solvent:
• Polar protic (H₂O, alcohols): stabilize carbocations, favor SN1/E1
• Polar aprotic (acetone, DMSO): leave nucleophile more reactive, favor SN2

Ultimate Decision Matrix

Substrate	Strong, Unhindered Base/Nuc	Strong, Bulky Base	Weak Base/Strong Nuc	Weak Base/Weak Nuc
Methyl	SN2	SN2	SN2	No Reaction
Primary (1°)	SN2 (major), E2 (minor)	E2	SN2	No Reaction
Secondary (2°)	E2 (major), SN2 (minor)	E2	SN2	SN1, E1
Tertiary (3°)	E2	E2	SN1 (slow)	SN1, E1

Part V: Oxygen- and Sulfur-Containing Compounds

5.1: Alcohols - Synthesis and Reactions

Synthesis of Alcohols

Method	Starting Material	Reagent	Product Type
Reduction	Aldehydes	NaBH₄, LiAlH₄	Primary alcohols
Reduction	Ketones	NaBH₄, LiAlH₄	Secondary alcohols
Grignard + HCHO	Formaldehyde	R-MgX	Primary alcohols
Grignard + RCHO	Other aldehydes	R-MgX	Secondary alcohols
Grignard + Ketones	Ketones	R-MgX	Tertiary alcohols

Grignard Reactions: Powerful method for forming new C-C bonds. The Grignard reagent (R-MgX) acts as a carbanion equivalent.

Reactions of Alcohols

Dehydration to Alkenes:
• Strong acid (H₂SO₄): E1 mechanism via carbocation
• POCl₃/pyridine: E2 mechanism

Conversion to Alkyl Halides:
• H-X: SN1 for 3° alcohols, SN2 for 1° alcohols
• SOCl₂, PBr₃: SN2 pathway for 1° and 2° alcohols

Oxidation:
• 1° alcohols: PCC → aldehydes; CrO₃ → carboxylic acids
• 2° alcohols: PCC or CrO₃ → ketones
• 3° alcohols: No oxidation under normal conditions

Key Point: -OH is a poor leaving group but can be converted to a good one through protonation or replacement.

5.2: Ethers, Epoxides, and Their Relatives

Williamson Ether Synthesis

The most important method for ether synthesis - a classic SN2 reaction.

Mechanism:
RO⁻ + R'X → R-O-R' + X⁻
(Alkoxide attacks primary alkyl halide)

Limitation: Must use primary alkyl halides to avoid elimination. Alkoxide formed by deprotonating alcohol with strong base.

Epoxide Ring-Opening Reactions

High ring strain makes epoxides highly reactive toward nucleophilic attack.

Conditions	Mechanism Type	Control Factor	Attack Site	Stereochemistry
Base-Catalyzed	SN2-like	Steric hindrance	Less substituted C	Trans
Acid-Catalyzed	SN1-like	Electronic effects	More substituted C	Trans

Base-Catalyzed: Strong nucleophile attacks less hindered carbon (steric control)

Acid-Catalyzed: Protonation makes ring more electrophilic; weak nucleophile attacks carbon that better stabilizes positive charge (electronic control)

Unifying Framework: Base-catalyzed = "SN2-like" (steric control), Acid-catalyzed = "SN1-like" (electronic control)

Part VI: An Introduction to the Molecules of Life

6.1: Carbohydrates

Carbohydrate Fundamentals

Carbohydrates (sugars) are polyhydroxy aldehydes and ketones serving as energy sources and structural materials.

Classification:
• Simple sugars: Monosaccharides
• D/L notation: Based on configuration of chirality center farthest from carbonyl
• Fischer projections: Used to depict stereochemistry

Cyclic Forms and Mutarotation

In solution, monosaccharides exist predominantly as cyclic hemiacetals.

Cyclization Process:
1. Intramolecular reaction of -OH group with aldehyde/ketone
2. Creates new chirality center at anomeric carbon
3. Produces α and β anomers (diastereomers)

Mutarotation: Anomers interconvert in solution via open-chain form

Glycosidic Bonds: Acetal linkages connect monosaccharides to form disaccharides and polysaccharides (starch, cellulose).

6.2: Amino Acids and Proteins

Amino Acid Structure

Proteins are polymers of 20 common α-amino acids. Each contains:

Central carbon (α-carbon)
Amino group (-NH₂)
Carboxylic acid group (-COOH)
Hydrogen atom
Variable side chain (R-group)

Zwitterions: At physiological pH, amino acids exist as dipolar ions with protonated amino group (-NH₃⁺) and deprotonated carboxylate (-COO⁻).

Peptide Bond Formation

Amino acids link via amide bonds between carboxylate of one amino acid and amino group of another.

Terminology:
• Peptide bond: Specific amide linkage in proteins
• Peptides: Short chains of amino acids
• Proteins: Very long chains (macromolecules)

Biological Function: Proteins serve as enzymes, structural components, and signaling molecules - the machinery of life.

Final Synthesis: The Reaction Map Strategy

Master Strategy: Create a reaction map to visualize connections between functional groups and plan multi-step syntheses.

Reaction Map Benefits

Provides "big picture" view of organic synthesis
Shows pathways to convert one functional group to another
Enables retrosynthetic analysis
Most effective strategy for exam success

Example Synthetic Route:
Alkene → Ether
Path 1: Alkene → (hydration) → Alcohol → (Williamson synthesis) → Ether
Path 2: Alkene → (alkoxymercuration-demercuration) → Ether

Study Recommendation: Build and regularly review a comprehensive reaction map based on all reactions covered. This visual tool is invaluable for mastering organic synthesis.