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Oxidizing primary alcohols (R-CH₂-OH) to carboxylic acids (R-COOH) is one of the most fundamental and important transformations in organic synthesis.
This process typically involves two-electron oxidation, passing through an aldehyde (R-CHO) intermediate, and further oxidizing to the carboxylic acid. Therefore, the key to a successful reaction lies in: 1) ensuring the oxidizing agent can continue to oxidize the aldehyde; 2) preventing the aldehyde from volatilizing or undergoing side reactions during the intermediate stage.
Here are the main methods:
1. Potassium permanganate
Conditions: KMnO₄ in an alkaline (such as NaOH), neutral or weakly acidic aqueous solution, heated. Very potent, can directly oxidize primary alcohols to carboxylic acids (through aldehyde). It often causes the cleavage of unsaturated bonds such as alkenes, with poor selectivity. It generates a large amount of MnO₂ sludge, and the post-treatment is troublesome. Suitable for simple substrates with low tolerance to functional groups, or situations where alkenes need to be oxidized simultaneously.
2. Jones reagent
Conditions: Chromium trioxide (CrO₃) in a dilute sulfuric acid aqueous solution (or a mixture of acetone and water) at room temperature or 0°C. Classic, reliable, and widely used. Can efficiently oxidize primary alcohols to carboxylic acids, usually not remaining at the aldehyde stage. Not suitable for substrates sensitive to acids (such as acetal, TBS ether, etc.) or allyl alcohol/benzyl alcohol (which may undergo peroxidation). Chromium (VI) is highly toxic and causes severe environmental pollution. Modern laboratories have tried to avoid using it. Suitable for aliphatic or simple aromatic primary alcohols that can tolerate acidic conditions.
3. TEMPO/sodium hypochlorite system
Conditions: Catalytic amount of TEMPO ((2,2,6,6-tetramethylpiperidine-1-oxyl radical), chemically measured amount of NaClO as the main oxidant, KBr as a co-catalyst, in a pH 9-10 water/organic two-phase system (such as CH₂Cl₂/H₂O), at 0-10°C. Mechanism: TEMPO acts as an oxidation-reduction mediator, with extremely high selectivity.温和、高效、高选择性。Usually only oxidizes primary alcohols to carboxylic acids， does not attack secondary alcohols， alkenes， amines and other sensitive groups. The reaction is rapid， and post-treatment is simple. pH control is key (commonly using NaHCO₃ or NaOH to adjust). Using Oxone (potassium peroxysulfate) or mCPBA instead of NaClO， the conditions are more mild. Suitable for sugar chemistry， natural products， and the preferred method for later functionalization of complex molecules. Especially suitable for substrates sensitive to acids and bases.
