Oxidation of Alcohols to Aldehydes or Ketones: Oxidizing Reagents
Among others, chromium(VI) reagents (chromium trioxide, chromic acid, chromates), manganese(IV) oxide (manganese dioxide), halogen compounds (chlorine, hypochloric acid), and dimethyl sulfoxide are commonly used as oxidizing reagents.
- Oxidation of of primary alcohols
| Sodium dichromate Na2Cr2O7
in aqueous H2SO4
(Jones reagent)|| Oxidizes alcohol to aldehyde. The problem of further oxidation to
carboxylic acid caused by the presence of water can be avoided for volatile alcohols in most cases by distilling the alcohols from the reaction mixture. Very often, it is more favorable to use acetic acid instead of sulfuric acid. |
| Pyridinium chlorochromate (PCC) || PCC is prepared from pyridine, chromium trioxide and hydrochloric acid. Since PCC is soluble in organic solvents, primary alcohols are oxidized in excellent yields to aldehydes in the absence of water. |
| Pyridinium dichromate (PDC) (C5H5NH)2Cr2O7
||Reaction of pyridine with chromium trioxide and a small amount of water yields pyridinium dichromate. This reagent dissolved in DMF or suspended in dichloromethane transforms primary allylic alcohols into the corresponding aldehydes. Depending on reaction conditions, saturated alcohols yield either aldehyde or carboxylic acid.
| Chromium trioxide-pyridine complex CrO3 · 2
C5H5N (Collins reagent) || Similar to PCC and PDC, this oxidizing reagent selectively oxidizes, for example, unsaturated primary alcohols to aldehydes without attacking the C=C double bond. |
| Manganese dioxide (MnO2)
|| Compared to potassium permanganate, this reagent is very useful because it preferably attacks allylic and benzylic hydroxy groups. Active manganese dioxide is prepared by a disproportionation reaction between manganese(II) sulfate and potassium permanganate and sodium hydroxide. The reactivity depends on the mode of preparation and the water content. |
| Hypochlorous acid HOCl ||Instead of chromium reagents, hypochloric acid in the form of the inexpensive, less poisonous, and easier to dispose of sodium hypochlorite can be used for the oxidation of primary and secondary alcohols to aldehydes and ketones, respectively. The reaction is carried out in a two-phase system (water/dichloromethane) in the presence of the stable radical 2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPO), KBr and NaHCO3
. The real catalyst (2,2,6,6-tetramethyl-1-oxo-piperidinium ion) which is formed reversibly during the reaction from TEMPO is responsible for the dehydrogenation of the alcohol. The resulting piperidinol derivative is then oxidized again by HOCl. Since C=C double bonds can add HOCl, they interfer with the oxidation of unsaturated alcohols.
| Catalytical dehydrogenation ||Suitable catalysts are metallic silver, copper, copper chromium dioxide, and zinc oxide. The dehydrogenation is highly endotherm. However, burning the hydrogen generated during the reaction with air generates a highly exotherm reaction (autotherm dehydrogenation).
| Anodic oxidation |
- Oxidation of secondary alcohols
|Jones reagent||Simple alcohols bearing no other functionality are dissolved in acetone and the stirred solution is "titrated" with the reagent at 15-20°C. The reaction is fast and complete. The acetone solution can be decanted from the heavy precipitate consisting of green chromium salts. Even unsaturated alcohols can be oxidized selectively at the hydroxy group by this methodology. |
|Chromium trioxide-pyridine complex||see above|
|Hypochloric acid||see above|
|Ruthenium tetroxide (RuO4) or TRAP (NPr4
||Reagent for special cases for which other methods failed. However, this reagent is a very strong oxidizing agent that will attack C=C double bonds. TRAP = tetrapropyl ammonium perruthenate
|Dimethyl sulfoxide (DMSO) in combination with electrophilic reagents||A mixture of DMSO and dicyclohexylcarbodiimide, acetic anhydride, trifluoroacetic anhydride, oxalyl chloride, or sulfur trioxide oxidizes alcohol to ketones. DMSO is activated by the electrophile to facilitate addition of the alcohol. Presumably, electrophilic attack by either of the reagents at the oxygen atom of the sulfoxide generates an alkoxysulfonium ylid intermediate . (Name reactions: Pfitzner-Moffat oxidation, Swern oxidation).|
|Dimethyl sulfide with N-chlorosuccinimide||This methodology allows for the oxidation of alcohols under very mild conditions. Dimethyl sulfide reacts with N-chlorosuccinimide to generate a chlorosulfonium ion which subsequently reacts with the alcohol. Elimination of dimethyl sulfide in the presence of a weak base completes the oxidation.|
|DMSO and chlorine||Similar to the reaction of DMSO with N-chlorosucinimide, the adduct formed at low temperature reacts with the alcohol to form a ketone and DMSO. |
|Aluminum alkoxide and carbonyl compound (Oppenauer oxidation)||Nowadays, this older methodology is less important. The Oppenaur oxidation is the reverse reaction of the Meerwein-Pondorff-Verley reduction. The alcohol to be oxidized is heated in the presence of aluminum alkoxide and a carbonyl compound that acts as a hydrogen acceptor.|
|Catalytical dehydrogenation||see above|
|Anodic oxidation||see above|