| Pinnick oxidation | |
|---|---|
| Named after | Harold W. Pinnick |
| Reaction type | Organic redox reaction |
ThePinnick oxidation is anorganic reaction by whichaldehydes can be oxidized into their correspondingcarboxylic acids usingsodium chlorite (NaClO2) under mildacidic conditions. It was originally developed by Lindgren and Nilsson.[1] The typical reaction conditions used today were developed by G. A. Kraus.[2][3] H.W. Pinnick later demonstrated that these conditions could be applied to oxidize α,β-unsaturated aldehydes.[4] There exist many different reactions to oxidize aldehydes, but only a few are amenable to a broad range offunctional groups. The Pinnick oxidation has proven to be both tolerant of sensitive functionalities and capable of reacting withsterically hindered groups. This reaction is especially useful for oxidizing α,β-unsaturated aldehydes, and another one of its advantages is its relatively low cost.[4][5]
The proposedreaction mechanism involveschlorous acid as the active oxidant, which is formed under acidic conditions from chlorite.
First, the chlorous acid adds to the aldehyde. Then resulting structure undergoes apericyclic fragmentation in which the aldehyde hydrogen is transferred to an oxygen on the chlorine, with the chlorine group released ashypochlorous acid (HOCl).[6]
The HOCl byproduct, itself a reactive oxidizing agent, can be a problem in several ways.[6] It can destroy the NaClO2 reactant:
making it unavailable for the desired reaction. It can also cause other undesiredside reactions with the organic materials. For example, HOCl can react with double bonds in the organic reactant or product via ahalohydrin formation reaction.
To prevent interference from HOCl, ascavenger is usually added to the reaction to consume the HOCl as it is formed. For example, one can take advantage of the propensity of HOCl to undergo this addition reaction by adding a sacrificial alkene-containing chemical to the reaction mixture. This alternate substrate reacts with the HOCl, preventing the HOCl from undergoing reactions that interfere with the Pinnick reaction itself.2-Methyl-2-butene is often used in this context:
Resorcinol andsulfamic acid are also common scavenger reagents.[6][7]
Hydrogen peroxide (H2O2) can be used as HOCl scavenger whose byproducts do not interfere in the Pinnick oxidation reaction:
In a weaklyacidic condition, fairly concentrated (35%) H2O2 solution undergoes a rapid oxidative reaction with no competitive reduction reaction of HClO2 to form HOCl.
Chlorine dioxide reacts rapidly with H2O2 to formchlorous acid.
Also the formation ofoxygen gives good indication of the progress of the reaction. However, problems sometimes arise due to the formation ofsinglet oxygen in this reaction, which may oxidize organic materials (i.e. theSchenck ene reaction). DMSO has been used instead of H2O2 to oxidize reactions that do not produce great yields using only H2O2. Mostly electron rich aldehydes fall under this category.[7] (See Limitation below)
Also, solid-supported reagents such as phosphate-bufferedsilica gel supported bypotassium permanganate and polymer-supported chlorite have been prepared and used to convert aldehydes to carboxylic acid without having to do conventional work-up procedures. The reaction involves the product to be trapped on silica gel as their potassium salts. Therefore, this procedure facilitates easy removal of neutral impurities by washing withorganic solvents.[8]
The reaction is highly suited for substrates with many group functionalities. β-aryl-substituted α,β-unsaturated aldehydes works well with the reaction conditions. Triple bonds directly linked to aldehyde groups or inconjugation with other double bonds can also be subjected to the reaction.[7][9]Hydroxides,epoxides, benzylethers,halides includingiodides and even stannanes are quite stable in the reaction.[7][9][10][11] The examples of the reactions shown below also show that the stereocenters of the α carbons remain intact while double bonds, especially trisubstituted double bonds do not undergoE/Z–isomerization in the reaction.
Lower yields are obtained for reactions involvingaliphatic α,β-unsaturated and more hydrophilic aldehydes. Double bonds and electron-rich aldehyde substrates can lead to chlorination as an alternate reaction. The use of DMSO in these cases gives better yield. Unprotectedaromaticamines andpyrroles are not well suited for the reactions either. In particular, chiral α-aminoaldehydes do not react well due to epimerization and because amino groups can be easily transformed to their correspondingN-oxides. Standardprotective group approaches, such as the use oft-BOC, are a viable solution to these problems.[12]
Thioethers are also highly susceptible to oxidation. For example, Pinnick oxidation of thioanisaldehyde gives a high yield of carboxylic acid products, but with concomitant conversion of the thioether to thesulfoxide orsulfone.[7]
