Common Organic Reactions

Why This Matters

Organic reactions are the vocabulary of molecular transformation—and on your exam, you're being tested on your ability to predict products, explain mechanisms, and choose the right reaction for a given synthesis problem. These reactions aren't random; they follow predictable patterns based on nucleophilicity, electrophilicity, substrate structure, and reaction conditions. Master the underlying logic, and you'll be able to tackle any mechanism question thrown at you.

The reactions in this guide represent the core toolkit of organic synthesis. From building carbon-carbon bonds to interconverting functional groups, each reaction type illustrates fundamental principles like carbocation stability, stereoelectronic effects, and kinetic vs. thermodynamic control. Don't just memorize reagents and products—know why each reaction proceeds the way it does and what concept it demonstrates.

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Substitution and Elimination: Competing Pathways

These reactions share a common starting point—an alkyl halide or similar substrate—but diverge based on nucleophile strength, base strength, substrate structure, and solvent choice. Understanding when substitution wins over elimination (and vice versa) is one of the most heavily tested skills in organic chemistry.

Nucleophilic Substitution (SN1 and SN2)

• SN2 is a concerted, one-step mechanism—the nucleophile attacks as the leaving group departs, resulting in inversion of configuration (Walden inversion)
• SN1 proceeds through a carbocation intermediate—the rate-determining step is unimolecular ionization, leading to racemization at the stereocenter
• Substrate structure determines the pathway—primary substrates favor SN2 (less steric hindrance), while tertiary substrates favor SN1 (stable carbocation)

Elimination (E1 and E2)

• E2 is a concerted process requiring anti-periplanar geometry—strong bases abstract a proton while the leaving group departs simultaneously, forming an alkene
• E1 shares the carbocation intermediate with SN1—weak bases and polar protic solvents favor this stepwise pathway
• Zaitsev's rule governs regioselectivity—the more substituted (more stable) alkene typically predominates unless steric factors favor the Hofmann product

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Addition Reactions: Building Complexity from Unsaturation

Addition reactions transform $\pi$ bonds into $\sigma$ bonds, converting alkenes and alkynes into more saturated products. The key is understanding electrophilic attack, carbocation intermediates, and stereochemical outcomes.

Addition to Alkenes

• Electrophilic addition follows Markovnikov's rule—the electrophile (often $H^+$) adds to the less substituted carbon, placing the carbocation on the more stable position
• Stereochemistry depends on the mechanism—halogenation proceeds through a cyclic halonium ion giving anti addition, while hydroboration-oxidation gives syn addition
• Common reactions include hydrohalogenation, halogenation, and hydration—each with predictable regiochemistry and stereochemistry based on intermediate stability

Diels-Alder Reaction

• This [4+2] cycloaddition forms six-membered rings in one step—a conjugated diene reacts with a dienophile through a concerted, pericyclic mechanism
• The reaction is stereospecific and follows endo selectivity—cis dienophile substituents remain cis in the product, and secondary orbital interactions favor the endo transition state
• Electronic matching matters—electron-rich dienes paired with electron-poor dienophiles (or vice versa) accelerate the reaction dramatically

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Aromatic Reactions: Preserving the Ring

Aromatic compounds undergo substitution rather than addition to maintain their stabilizing aromaticity. Electrophilic aromatic substitution (EAS) is the key mechanism, and directing effects determine where new substituents land.

Electrophilic Aromatic Substitution

• The mechanism proceeds through a resonance-stabilized arenium ion (sigma complex)—the electrophile attacks the ring, temporarily disrupting aromaticity before a proton is lost to restore it
• Substituent directing effects are critical—electron-donating groups ($-OH$, $-NH_2$) are ortho/para directors and activators, while electron-withdrawing groups ($-NO_2$, $-CF_3$) are meta directors and deactivators
• Common electrophiles require activation—halogenation needs Lewis acid catalysts ($FeBr_3$), nitration uses $NO_2^+$ from mixed acids, and Friedel-Crafts reactions generate carbocations or acylium ions

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Carbonyl Chemistry: The Heart of Organic Synthesis

Carbonyl compounds are electrophilic at carbon and can undergo nucleophilic addition, substitution at the carbonyl, or reactions at the $\alpha$-carbon. These reactions form the basis of most carbon-carbon bond-forming strategies.

Aldol Condensation

• The aldol reaction forms $\beta$-hydroxy carbonyl compounds—an enolate nucleophile attacks another carbonyl, creating a new C–C bond
• Dehydration gives $\alpha,\beta$-unsaturated carbonyls—heating or acid/base treatment eliminates water, forming a conjugated system stabilized by resonance
• Crossed and intramolecular variants are synthetically powerful—controlling which enolate forms and which carbonyl is attacked is key to selectivity

Grignard Reaction

• Grignard reagents ($RMgX$) are powerful carbon nucleophiles—they attack carbonyl carbons to form new C–C bonds, yielding alcohols after aqueous workup
• Product class depends on the carbonyl substrate—formaldehyde gives primary alcohols, aldehydes give secondary alcohols, and ketones give tertiary alcohols
• Anhydrous conditions are essential—Grignard reagents react violently with water, destroying the reagent before it can attack the carbonyl

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Oxidation and Reduction: Interconverting Functional Groups

These reactions change the oxidation state of carbon without forming new C–C bonds. Mastering oxidation levels—alkane → alcohol → aldehyde/ketone → carboxylic acid—helps you predict products and plan syntheses.

Oxidation of Alcohols

• Primary alcohols oxidize to aldehydes or carboxylic acids—PCC (pyridinium chlorochromate) stops at the aldehyde, while $CrO_3$/$H_2SO_4$ (Jones oxidation) or $KMnO_4$ pushes to the acid
• Secondary alcohols oxidize to ketones—no further oxidation occurs because there's no C–H bond on the carbonyl carbon
• Tertiary alcohols cannot be oxidized—lacking a hydrogen on the carbinol carbon, they resist oxidation under standard conditions

Reduction of Carbonyl Compounds

• $LiAlH_4$ is a powerful, non-selective reducing agent—it reduces aldehydes, ketones, esters, and carboxylic acids to alcohols
• $NaBH_4$ is milder and more selective—it reduces aldehydes and ketones but leaves esters and acids untouched
• The mechanism involves hydride delivery to the electrophilic carbonyl carbon—a tetrahedral alkoxide intermediate forms, then protonation gives the alcohol

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Carboxylic Acid Derivatives: Acyl Transfer Reactions

Carboxylic acids and their derivatives undergo nucleophilic acyl substitution, where a nucleophile replaces the leaving group while preserving the carbonyl. Reactivity follows the leaving group ability: acyl chloride > anhydride > ester > amide.

Esterification

• Fischer esterification combines a carboxylic acid and alcohol under acid catalysis—protonation activates the carbonyl, the alcohol attacks, and water is lost
• The reaction is reversible and equilibrium-controlled—Le Chatelier's principle applies; remove water or use excess alcohol to drive the reaction forward
• Transesterification exchanges one alcohol for another—useful in biodiesel production and polymer chemistry

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Quick Reference Table

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Self-Check Questions

1. Which two reaction types share a carbocation intermediate, and how does this affect the competition between them when treating a tertiary alkyl halide with a weak nucleophile?

2. Compare the stereochemical outcomes of SN2 and electrophilic bromination of an alkene. What mechanistic feature explains why one gives inversion and the other gives anti addition?

3. A student wants to convert a primary alcohol to an aldehyde without over-oxidizing to the carboxylic acid. Which reagent should they choose, and why does it stop at the aldehyde?

4. Explain why electron-donating groups on a benzene ring direct incoming electrophiles to the ortho and para positions. How does resonance stabilization of the sigma complex account for this?

5. You need to form a new C–C bond to convert benzaldehyde into a secondary alcohol. Compare the Grignard approach with the aldol approach—which would you choose for this specific transformation, and why?