Identifying the right reagents for an organic chemistry reaction depends on recognizing the type of transformation taking place: what functional group you’re starting with, what you’re converting it to, and whether selectivity matters. Below is a practical guide to the reagents required for the most common reaction types you’ll encounter, organized by the transformation involved.
Oxidation of Alcohols
Primary alcohols can be oxidized to either aldehydes or carboxylic acids, and the reagent setup determines which product you get. To stop at the aldehyde, use pyridinium chlorochromate (PCC) in dichloromethane. PCC is a mild, selective oxidizing agent that won’t push the reaction further. To go all the way to the carboxylic acid, use sodium or potassium dichromate acidified with dilute sulfuric acid, heated under reflux with an excess of the oxidizing agent. Jones reagent (chromium trioxide in aqueous sulfuric acid and acetone) accomplishes the same full oxidation.
The key distinction is reaction conditions. Getting an aldehyde from a primary alcohol with dichromate requires using excess alcohol and distilling the aldehyde off as soon as it forms, preventing further oxidation. For the carboxylic acid, you leave the aldehyde intermediate in the mixture and let it keep reacting. Secondary alcohols oxidize to ketones with any of these reagents, and since ketones resist further oxidation, selectivity isn’t an issue. Tertiary alcohols don’t oxidize at all under these conditions.
Reduction of Carbonyls and Carboxylic Acids
Two reducing agents dominate this category, and their strength determines what they can reduce. Lithium aluminum hydride (LiAlH4) is the stronger of the two. It reduces carboxylic acids to primary alcohols, esters to primary alcohols, and aldehydes or ketones to alcohols. Sodium borohydride (NaBH4) is milder. It handles aldehydes and ketones just fine, converting them to alcohols, but it is not strong enough to reduce carboxylic acids or esters.
For a more selective transformation, DIBAL-H (diisobutylaluminum hydride) converts esters to aldehydes when the reaction is run at -78°C. That low temperature is critical: it prevents the aldehyde product from reacting further. At warmer temperatures, DIBAL-H would push the reduction all the way to the alcohol, just like LiAlH4. So the reagent choice here is really about how far down the reduction pathway you want to go. NaBH4 for simple carbonyl-to-alcohol conversions, LiAlH4 for stubborn substrates like acids and esters, and DIBAL-H when you need to stop at the aldehyde stage.
Alkene Hydration
Adding water across a double bond requires different reagents depending on where you want the hydroxyl group to end up. Acid-catalyzed hydration uses dilute sulfuric acid (or another strong acid) and water, and follows Markovnikov’s rule: the OH attaches to the more substituted carbon. Oxymercuration-demercuration achieves the same Markovnikov selectivity but avoids carbocation rearrangements. It uses mercuric acetate in water for the first step, then sodium borohydride to remove the mercury.
For anti-Markovnikov hydration, where the OH ends up on the less substituted carbon, you need hydroboration-oxidation. The first step uses borane (BH3, often as a complex with THF) to add boron across the double bond. The second step treats the resulting organoborane with hydrogen peroxide and sodium hydroxide to replace the boron with a hydroxyl group. This two-step sequence requires stoichiometric amounts of the borane reagent.
Grignard Reactions and Carbon-Carbon Bonds
Forming a Grignard reagent requires three things: an alkyl or aryl halide, magnesium metal, and anhydrous diethyl ether (or THF) as the solvent. The halide reacts with magnesium in the ether to form the organomagnesium compound (RMgBr, for example). The solvent coordinates to the magnesium and stabilizes the reagent, which is why ether or THF is essential rather than optional.
The single most important condition is that everything must be completely dry. The carbon-metal bond in a Grignard reagent is extraordinarily basic, and even trace moisture will destroy it by protonation. The solvent must be anhydrous, the glassware must be oven-dried, and moist air cannot be allowed into the reaction flask. Once formed, the Grignard reagent reacts with carbonyl compounds (aldehydes, ketones, esters) to form new carbon-carbon bonds, followed by an acidic water workup to protonate the resulting alkoxide.
Electrophilic Aromatic Substitution
Each type of electrophilic aromatic substitution has its own reagent-catalyst pair:
- Bromination: Br2 with FeBr3 as a Lewis acid catalyst. The catalyst activates the bromine to generate a stronger electrophile.
- Chlorination: Cl2 with FeCl3 or AlCl3 as the Lewis acid catalyst.
- Nitration: Concentrated nitric acid (HNO3) with concentrated sulfuric acid (H2SO4). The sulfuric acid protonates nitric acid to generate the nitronium ion, which is the actual electrophile that attacks the ring.
- Friedel-Crafts alkylation: An alkyl chloride (RCl) with aluminum chloride (AlCl3) as the catalyst.
- Friedel-Crafts acylation: An acyl chloride or acid anhydride, again with AlCl3 as the catalyst.
One important exception: highly activated rings (those bearing methoxy, hydroxyl, or amine groups) are reactive enough for halogenation without the Lewis acid catalyst. To monohalogenate phenol, for instance, you run the reaction in a nonpolar solvent like carbon tetrachloride with no added catalyst.
Substitution and Elimination Reactions
For substitution and elimination reactions involving alkyl halides, the reagent you choose and the solvent you use together determine which pathway dominates.
SN2 reactions need a strong nucleophile and a polar aprotic solvent. Common polar aprotic solvents include DMSO, DMF, acetone, and acetonitrile. These solvents dissolve ionic reagents but don’t solvate the nucleophile heavily, leaving it free to attack. Good nucleophiles for SN2 include thiolates, azide, cyanide, and halide ions. Primary substrates work best, secondary substrates are borderline, and tertiary substrates won’t undergo SN2 at all.
SN1 reactions favor polar protic solvents like water, methanol, or ethanol. These solvents stabilize the carbocation intermediate that forms when the leaving group departs. Tertiary substrates are ideal for SN1 because they form the most stable carbocations. The nucleophile can be weak since the rate-determining step is carbocation formation, not nucleophilic attack.
E2 elimination requires a strong, bulky base (like potassium tert-butoxide) and is also favored by polar protic solvents when competing with SN2. When a secondary alkyl halide is treated with a strong base like sodium hydroxide, switching from a polar aprotic solvent to a polar protic solvent can shift the balance from substitution toward elimination. E1 elimination, like SN1, occurs in polar protic solvents with tertiary substrates and typically competes directly with SN1.
Amide and Ester Formation
Converting a carboxylic acid to an ester (Fischer esterification) requires an alcohol and an acid catalyst, typically concentrated sulfuric acid or p-toluenesulfonic acid, with heating. The acid catalyst protonates the carbonyl oxygen and makes the carbon more electrophilic for nucleophilic attack by the alcohol.
Forming amides from carboxylic acids and amines is thermodynamically favorable but kinetically slow, which is why coupling reagents are commonly used. Reagents like DCC (dicyclohexylcarbodiimide), EDC, CDI (carbonyldiimidazole), and T3P activate the carboxylic acid so the amine can attack more readily. In peptide chemistry, uronium reagents like HATU and HBTU have been widely used, though they carry safety concerns including potential for anaphylactic reactions on skin contact. An alternative classical approach is to convert the acid to an acid chloride first (using thionyl chloride or oxalyl chloride), then react that with the amine.
Palladium-Catalyzed Cross-Coupling
Suzuki, Heck, and related coupling reactions all require a palladium catalyst, but they differ in their other reagent requirements. A Suzuki coupling joins an aryl halide with an organoboron compound (a boronic acid or boronate ester) and needs a base, typically an inorganic phosphate or carbonate. The palladium source is often Pd(PPh3)4 or Pd(OAc)2 with added phosphine ligands. A Heck reaction couples an aryl halide with an alkene and uses an amine base. The choice of base can actually steer the reaction pathway: amines favor Heck products, carbonates favor Sonogashira products, and phosphates favor Suzuki products when using the same palladium catalyst.
Optimization of these reactions involves tuning several variables simultaneously. Ligand choice, base equivalents, temperature, and solvent all interact, and even small changes in stoichiometry can shift the yield or selectivity significantly. In a stereoselective Suzuki coupling, for example, varying the ligand and temperature changes the ratio of geometric isomers in the product. Getting good yields often requires systematic adjustment of reagent equivalents, since excess of one component can promote unwanted side reactions.
Handling Reactive Reagents Safely
Several reagents common in organic synthesis are pyrophoric (they ignite on contact with air) or water-reactive. Organolithium compounds like t-butyllithium and metal hydrides like sodium hydride fall into this category. These reagents should ideally be handled inside a glovebox under inert atmosphere. When that isn’t possible, work inside a chemical fume hood using syringes and cannulas that have been dried and purged with inert gas like nitrogen or argon.
Sodium hydride is typically sold as a dispersion in mineral oil to prevent air exposure. Before use, the oil is washed away with dry hexane injected through a septum, and the hexane washings are carefully quenched with isopropanol. A critical rule: always add the metal hydride slowly to the anhydrous solvent already in the flask, never the other way around. Keep powdered lime or dry sand within reach to smother any spill. Standard nitrile gloves work for small quantities, but flame-resistant lab coats are required whenever you’re working with these materials.