Pinnick oxidation

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The Pinnick oxidation is also known as the Lindgren oxidation. It is an organic reaction by which aldehydes can be oxidized into their corresponding carboxylic acids, and it was originally developed by Lindgren and Nilsson.[1] The typical reaction conditions used today were developed by G. A. Kraus, and H.W. Pinnick later proved that these conditions were generally applicable to a wide variety of systems.[2][3] There exist many different reactions to oxidize aldehydes, but only a few are amenable to a broad range of functional groups. The Pinnick oxidation has proven to be both tolerant of sensitive functionalities and capable of reacting with sterically 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]

PinnickOxidationReaction

[5]

Mechanism[edit]

The following reaction mechanism has been proposed for the Pinnick Oxidation. This mechanism results in the formation of HOCl, a reactive by-product that can consume the remaining NaClO2. Therefore, the use of scavengers to actively remove these byproducts during the reaction is required.[6] (See Side Reactions below)

PinnickOxidationMechanism

this is done by oxidation reaction of barium sulphate .

Side Reaction and Scavenging[edit]

Aside from the fact that NaClO2 is consumed by side reactions with it, hypochlorite ions can also cause other problems. The HOCl/Cl- redox pair is a more powerful oxidant than ClO2-/HOCl, which means that it can react with olefin double bonds. To avoid such problems, HOCl scavengers such as 2-methyl-2-butene, resorcinol and sulfamic acid can be used in the reaction. The reaction by which 2-methyl-2-butene traps HOCl is depicted below.[7][6]

SideReactionAndScavenging

Modification[edit]

H2O2 have been used as HOCl scavenger without the formation of side products.

HOCl + H2O2

In a weakly acidic condition, 35% of H2O2 undergoes rapid oxidative reaction with no competitive reduction reaction of HClO2 to form HOCl. The Chlorine dioxide reacts rapidly with H2O2 to form chlorous acid.

HClO2 + H2O2

Also the formation of oxygen gives good indication of the progress of the reaction. DMSO has been used of instead of H2O2 to oxidize reactions that do not produce great yields using only H2O2. Mostly electron rich aldheydes fall under this category.[7] (See Limitation below)

Also, solid-supported reagents such as phosphate-buffered silica gel supported by potassium 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 with organic solvents.[8]

Scope[edit]

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 in conjugation with other double bonds can also be subjected to the reaction.[9][7] Hydroxides, epoxides, benzyl ethers, halides including iodides and even stannanes are quite stable in the reaction.[10][11][7][9] The examples of the reactions shown below also show that the stereocenters of the α carbons remain intact while double bonds, especially trisubsituted double bonds do not undergo E/Z–isomerization in the reaction.

Scope

Limitations[edit]

Lower yields are obtained for reactions involving aliphatic α,β-unsaturated and more hydrophilic aldehydes. Electron donor group in β-position can result in chlorination of the double bond. The presence of isolated double or electron rich substrates give rise to similar problems. The use of DMSO in these cases gives better yield. Unprotected aromatic amines and pyrrols are not well suited for the reactions either. Thiobenzaldehyes follows oxidation to sulfoxides and sulfones.α-Aminoaldehydes do not react well due to epimerization and because amino groups can be easily transformed to their corresponding N-oxides. Protection of the amino group can be used for the oxidation of the amino aldehydes.[12][7]

Limitations

Synthetic Uses[edit]

Zaragozic acid is a potent squalene synthase inhibitor that can reduce the side effects caused by cholesterol inhibiting drugs which can also interfere with the production of important steroids. The total synthesis of Zaragozic acid applied by A. Armstrong was possible through Pinnick Oxidation. Different oxidation methods such as Jones oxidation, modified Ley Oxidation were also applied. However, the efforts resulted in a mixture of products. A good yield with good purity could be obtained via Pinnick Oxidation.[13][6]

zaragozic acid

See also[edit]

Sodium Chlorite

References[edit]

  1. ^ Lindgren, Bengt O.; Nilsson, Torsten; Husebye, Steinar; Mikalsen, ØYvind; Leander, Kurt; Swahn, Carl-Gunnar (1973). "Preparation of Carboxylic Acids from Aldehydes (Including Hydroxylated Benzaldehydes) by Oxidation with Chlorite". Acta Chemica Scandinavica 27: 888. doi:10.3891/acta.chem.scand.27-0888. 
  2. ^ George A. Kraus; Bruce Roth (1980). "Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system". The Journal of Organic Chemistry 45: 4825. doi:10.1021/jo01312a004. 
  3. ^ George A. Kraus; Michael J. Taschner (1980). "Model studies for the synthesis of quassinoids. 1. Construction of the BCE ring system". The Journal of Organic Chemistry 45: 1175. doi:10.1021/jo01294a058. 
  4. ^ Bal, B. S.; Childers, W.E.; Pinnick, H.W. (1981). "Oxidation of α,β-Unsaturated Aldehydes". Tetrahedron 37: 2091–2096. doi:10.1016/S0040-4020(01)97963-3. 
  5. ^ Mundy, B.J; Michael G. Ellerd; Frank G. Favaloro (2005). Name reactions and reagents in organic synthesis. John Wiley & Sons. ISBN 978-0-471-22854-7. 
  6. ^ a b c Corey, E.J; K.C. Nicolaou (2005). Strategic Applications of Named Reactions. Elsevier, Inc. ISBN 978-7-03-019190-8. 
  7. ^ a b c d e Dalcanale, E; Montanari, F; (1986). "Selective Oxidation of Aldehydes to Carboxylic Acids with Sodium Chlorite-Hydrogen Peroxide". J. Org. Chem 51: 567–569. doi:10.1021/jo00354a037. 
  8. ^ Takemoto, T.; Yasuda, K.; Ley, S.V. (2001). "Solid-Supported Reagents for the Oxidation of Aldehydes to Carboxylic Acids". Synlett 10: 1555–1556. doi:10.1055/s-2001-17448. 
  9. ^ a b Raach, A.; Reiser, O. (2000). "Sodium Chlorite-Hydrogen Peroxide, a Mild and Selective Reagent for the Oxidation of Aldehydes to Carboxylic Acids". J. Prakt. Chem. 342: 605–608. doi:10.1002/1521-3897. 
  10. ^ Ishihara, J. ; Hagihara, K.; Chiba, H. ; Ito, K. ; Yanagisawa, Y.; Totani, K; Tadano, K. (2000). "Synthetic studies of viridenomycin. Construction of the cyclopentene carboxylic acid part". Tetrahedron. Lett. 41: 1771–1774. doi:10.1016/S0040-4039(00)00013-7. 
  11. ^ Kuramochi, K.; Nagata, S. ; Itaya, H.; Takao, H.; Kobayashi, S. (1999). "Convergent Total Synthesis of epolactaene: application of bridgehead oxiranyl anion strategy". Tetrahedron. Lett. 40: 7371–7374. doi:10.1016/S0040-4039(99)01512-9. 
  12. ^ Dehoux, C.; Fontaine, E.; Escudier, J.; Baltas, M.; Gorrichon, L. (1998). "Total Synthesis of Thymidine 2-Deoxypolyoxine C Analogue". J.Org. Chem. 63: 2601–2608. doi:10.1021/jo972116s. 
  13. ^ Armstrong, A.; Barsanti, P.A.; Jones, L.H.; Ahmed, G.; (2000). "Total Synthesis of (+)-Zaragozic Acid C". J.Org. Chem. 65: 7020–7032. doi:10.1021/jo000700m.