Organic Reactions Summary: A Comprehensive Guide to Major Reaction Types

Nucleophilic Substitution (SN1 and SN2)

Nucleophilic substitution replaces a leaving group on a carbon atom with an incoming nucleophile. The SN2 mechanism (substitution, nucleophilic, bimolecular) proceeds in a single concerted step: the nucleophile attacks the electrophilic carbon from the backside while the leaving group departs from the front. This requires an accessible carbon center, so SN2 is fastest with methyl and primary substrates, slower with secondary, and essentially impossible with tertiary substrates due to steric hindrance. SN2 reactions produce complete inversion of stereochemistry (Walden inversion) at the reaction center.

The SN1 mechanism (substitution, nucleophilic, unimolecular) proceeds in two steps: first the leaving group departs to form a carbocation intermediate, then the nucleophile attacks the carbocation. Because the rate-determining step (carbocation formation) depends only on the substrate concentration, SN1 reactions are favored by tertiary substrates (most stable carbocations), polar protic solvents (stabilize the carbocation and leaving group through solvation), and weak nucleophiles. SN1 reactions produce racemization because the planar carbocation can be attacked from either face, though often with a slight preference for inversion.

Key reactions in this category include alkyl halide reactions with nucleophiles (hydroxide, cyanide, azide, thiolate, halide exchange), Williamson ether synthesis, and conversion of alcohols to alkyl halides via tosylation followed by displacement.

Elimination (E1 and E2)

Elimination reactions remove a leaving group and a beta hydrogen from adjacent carbons to form a double bond (alkene). The E2 mechanism (elimination, bimolecular) is a concerted, one-step process requiring anti-periplanar geometry between the hydrogen and leaving group. E2 reactions are promoted by strong, bulky bases (like potassium tert-butoxide), high temperature, and secondary or tertiary substrates. They produce the more substituted alkene preferentially (Zaitsev rule) unless a very bulky base is used, which gives the less substituted alkene (Hofmann product).

The E1 mechanism (elimination, unimolecular) shares the same first step as SN1: ionization to form a carbocation. A base then removes a beta hydrogen to form the alkene. E1 is favored by tertiary substrates, polar protic solvents, weak bases, and high temperature. Because both SN1 and E1 proceed through the same carbocation intermediate, they often compete and give product mixtures.

The competition between substitution and elimination is governed by substrate structure, base/nucleophile strength and size, solvent, and temperature. Primary substrates with strong nucleophiles favor SN2. Tertiary substrates with strong bases favor E2. Tertiary substrates with weak nucleophiles in polar protic solvents give SN1/E1 mixtures, with higher temperature favoring elimination. These competition principles are among the most frequently tested concepts in organic chemistry.

Electrophilic Addition

Alkenes and alkynes are electron-rich at their pi bonds and react with electrophiles through addition reactions that break the pi bond and form two new sigma bonds. Hydrohalogenation (addition of HBr, HCl) follows Markovnikov rule: the hydrogen adds to the less substituted carbon, and the halide adds to the more substituted carbon, because the reaction proceeds through the more stable carbocation intermediate. Anti-Markovnikov addition is achieved using radical conditions (HBr with peroxides) or hydroboration-oxidation.

Halogenation (Br2, Cl2) adds two halogen atoms across the double bond through a cyclic halonium ion intermediate, giving anti addition (the two halogens end up on opposite faces of the former double bond). Hydration (H2O with acid catalyst) follows Markovnikov selectivity. Catalytic hydrogenation (H2 with Pd, Pt, or Ni catalyst) delivers both hydrogens to the same face of the double bond (syn addition), reducing the alkene to an alkane.

Alkyne additions follow similar principles but can be stopped at the mono-addition stage (giving a vinyl product) or carried through to double addition. Lindlar catalyst reduces alkynes to cis-alkenes (syn addition of H2), while dissolving metal reduction (Na in liquid NH3) gives trans-alkenes (anti addition). These selective partial reductions are powerful tools in synthesis for controlling alkene geometry.

Nucleophilic Addition to Carbonyls

Aldehydes and ketones react with nucleophiles through addition to the electrophilic carbonyl carbon. The nucleophile attacks, the pi bond breaks, and the oxygen becomes an alkoxide, which is protonated in the workup step. Hydride reduction (NaBH4, LiAlH4) gives alcohols. Grignard reagents and organolithium reagents give alcohols with new carbon-carbon bonds. Water gives hydrates (geminal diols). Alcohols give hemiacetals and acetals. Primary amines give imines. Secondary amines give enamines. Hydrogen cyanide gives cyanohydrins. Wittig reagents give alkenes (Wittig reaction).

Aldehydes are more reactive than ketones toward nucleophilic addition because of both steric factors (one hydrogen versus two alkyl groups flanking the carbonyl) and electronic factors (alkyl groups donate electron density to the carbonyl carbon, making it less electrophilic). Formaldehyde is the most reactive common carbonyl compound toward nucleophilic addition.

Nucleophilic Acyl Substitution

Carboxylic acid derivatives (acid chlorides, anhydrides, esters, amides) undergo substitution rather than simple addition because they have a leaving group on the carbonyl carbon. The mechanism involves nucleophilic attack to form a tetrahedral intermediate, followed by collapse of the intermediate with expulsion of the leaving group and regeneration of the carbonyl. The reactivity order follows leaving group ability: acid chlorides are the most reactive (chloride is an excellent leaving group), followed by anhydrides, esters, and amides (nitrogen is a very poor leaving group).

These reactions allow interconversion between carboxylic acid derivatives: acid chlorides can be converted to anhydrides, esters, or amides by reaction with the appropriate nucleophile. Fischer esterification converts carboxylic acids to esters under acid catalysis with an alcohol. Saponification hydrolyzes esters to carboxylate salts under basic conditions. Amide formation typically requires activation of the carboxylic acid (conversion to acid chloride or active ester) because direct reaction of an acid and amine produces a salt rather than an amide.

Electrophilic Aromatic Substitution

Aromatic rings react with electrophiles through a substitution mechanism that preserves aromaticity. The electrophile attacks the pi system to form a non-aromatic carbocation intermediate (sigma complex or arenium ion), then loss of a proton from the same carbon restores the aromatic ring. Common electrophilic aromatic substitution reactions include halogenation (Br2/FeBr3), nitration (HNO3/H2SO4), sulfonation (SO3/H2SO4), Friedel-Crafts alkylation (RCl/AlCl3), and Friedel-Crafts acylation (RCOCl/AlCl3).

Substituents already on the ring direct incoming electrophiles to specific positions. Electron-donating groups (alkyl, amino, hydroxyl, alkoxy) are ortho/para directors and activators, making the ring more reactive than benzene. Electron-withdrawing groups (nitro, cyano, carbonyl, sulfonyl) are meta directors and deactivators, making the ring less reactive. Halogens are the exception: they are deactivating (electron-withdrawing by induction) but ortho/para directing (electron-donating by resonance). These directing effects are essential for planning the synthesis of polysubstituted aromatic compounds.

Oxidation and Reduction

Oxidation in organic chemistry generally corresponds to increasing the number of bonds between carbon and oxygen (or other electronegative atoms) or decreasing the number of bonds between carbon and hydrogen. Reduction is the reverse. Primary alcohols can be oxidized to aldehydes (PCC, Dess-Martin, Swern) or to carboxylic acids (Jones, KMnO4). Secondary alcohols are oxidized to ketones. Alkenes can be oxidized to epoxides (mCPBA), diols (OsO4), or cleaved to carbonyl fragments (ozone, followed by reductive or oxidative workup).

Reduction of functional groups restores carbon-hydrogen bonds or breaks carbon-oxygen bonds. Catalytic hydrogenation (H2/Pd) reduces alkenes, alkynes, and aromatic nitro groups. LiAlH4 reduces carboxylic acids, esters, amides, aldehydes, ketones, and epoxides. NaBH4 selectively reduces aldehydes and ketones without affecting esters or carboxylic acids. Clemmensen reduction (Zn-Hg/HCl) and Wolff-Kishner reduction (N2H4/KOH) convert carbonyl groups all the way to methylene groups (C=O to CH2), which is useful for deoxygenation of Friedel-Crafts acylation products.

Enolate and Carbonyl Alpha-Carbon Chemistry

Carbonyl compounds with alpha hydrogens can be deprotonated by strong bases to form enolate ions, which are nucleophilic at the alpha carbon. Enolate alkylation with alkyl halides forms new carbon-carbon bonds at the alpha position. The aldol reaction combines two carbonyl molecules through enolate attack on a second carbonyl, giving a beta-hydroxy carbonyl that can dehydrate to an alpha,beta-unsaturated carbonyl (aldol condensation). The Claisen condensation is the analogous reaction for esters, producing beta-keto esters. Michael addition is the conjugate addition of an enolate to an alpha,beta-unsaturated carbonyl, forming a 1,5-dicarbonyl.

These reactions are the workhorses of carbon-carbon bond formation in synthesis. The malonic ester synthesis and acetoacetic ester synthesis use stabilized enolates for controlled alkylation and decarboxylation sequences. Crossed aldol and Claisen reactions require strategies to control which carbonyl acts as nucleophile and which acts as electrophile, typically using lithium diisopropylamide (LDA) for kinetic enolate formation or using one partner that lacks alpha hydrogens.

Radical Reactions

Free radical reactions involve species with unpaired electrons and proceed through initiation (radical generation, usually by heat or light), propagation (chain-carrying steps where radicals react with closed-shell molecules to produce new radicals), and termination (radical combination or disproportionation). Radical halogenation of alkanes replaces a C-H bond with a C-X bond, with selectivity favoring more substituted positions because tertiary radicals are more stable than secondary, which are more stable than primary.

Radical addition of HBr to alkenes gives anti-Markovnikov products because the bromine radical adds first, forming the more stable carbon radical. Radical polymerization chains together thousands of alkene monomers to form polyethylene, polypropylene, PVC, and polystyrene. Radical reactions also play important roles in combustion, atmospheric chemistry, and biological processes including lipid peroxidation and some enzyme mechanisms.