Pinnick oxidation
Encyclopedia
The Pinnick oxidation is also known as Lindgren oxidation
. It is an organic reaction
by which aldehydes can be oxidized into its corresponding carboxylic acid
, originally developed by Lindgren and Nilsson. The typical reaction condition used today was modified by G. A. Kraus even before Pinnick. Pinnick proved this condition as general. There are number of ways to oxidize the aldehydes however, only few reactions are endurable to the broad range of functional groups. One of such reaction is Pinnick Oxidation which can provide preferred transformation even to systems that contain sensitive functionalities or sterically hindered groups. This reaction is especially useful for oxidizing α-methylene aldehyde units. It is an inexpensive method for effectively oxidizing aldehydes in stereospecific manner. The reaction is named after chemist
H.W. Pinnick.
was proposed for Pinnick Oxidation. However, the mechanism follows formation of a by-product
that can cause a side reaction which can inevitably consume NaClO2. Therefore, the reaction requires the use of scavengers to be able to remove the by-products. (See Side Reactions below)
reacts with aldehydes under mild conditions to form carboxylic acids, side reactions can also occur. Aside, from the fact that NaClO2 are consumed by side reactions hypochlorite ions formed can also cause other problems. The redox pair HOCl/Cl- is a more powerful oxidant than ClO2-/HOCl which can react with double bonds in case of α,β-unsaturated aldehydes. To avoid such problems HOCl scavengers such as 2-Methyl-2-butene, resorcinol and sulfamic acids can be used in the reaction. The scavengers trap the HOCl ions as shown by reaction below inhibiting the formation ClO2- ions.
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
.
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. (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.
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 steroid
s. 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.
Lindgren oxidation
Lindgren oxidation named after Bengt O. Lindgren is a selective method for oxidizing aldehydes to carboxylic acids. It is often wrongly mentioned as Pinnick oxidation....
. It is an organic reaction
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
by which aldehydes can be oxidized into its corresponding carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
, originally developed by Lindgren and Nilsson. The typical reaction condition used today was modified by G. A. Kraus even before Pinnick. Pinnick proved this condition as general. There are number of ways to oxidize the aldehydes however, only few reactions are endurable to the broad range of functional groups. One of such reaction is Pinnick Oxidation which can provide preferred transformation even to systems that contain sensitive functionalities or sterically hindered groups. This reaction is especially useful for oxidizing α-methylene aldehyde units. It is an inexpensive method for effectively oxidizing aldehydes in stereospecific manner. The reaction is named after chemist
Chemist
A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...
H.W. Pinnick.
Mechanism
Following reaction mechanismReaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
was proposed for Pinnick Oxidation. However, the mechanism follows formation of a by-product
By-product
A by-product is a secondary product derived from a manufacturing process or chemical reaction. It is not the primary product or service being produced.A by-product can be useful and marketable or it can be considered waste....
that can cause a side reaction which can inevitably consume NaClO2. Therefore, the reaction requires the use of scavengers to be able to remove the by-products. (See Side Reactions below)
Side Reaction and Scavenging
Although sodium chloriteSodium chlorite
Sodium chlorite is a chemical compound used in the manufacture of paper.-Use:The main application of sodium chlorite is the generation of chlorine dioxide for bleaching and stripping of textiles, pulp, and paper. It is also used for disinfection of a few municipal water treatment plants after...
reacts with aldehydes under mild conditions to form carboxylic acids, side reactions can also occur. Aside, from the fact that NaClO2 are consumed by side reactions hypochlorite ions formed can also cause other problems. The redox pair HOCl/Cl- is a more powerful oxidant than ClO2-/HOCl which can react with double bonds in case of α,β-unsaturated aldehydes. To avoid such problems HOCl scavengers such as 2-Methyl-2-butene, resorcinol and sulfamic acids can be used in the reaction. The scavengers trap the HOCl ions as shown by reaction below inhibiting the formation ClO2- ions.
Modification
H2O2 have been used as HOCl scavenger without the formation of side products.In a weakly acidic condition, 35% of H2O2 undergoes rapid oxidative reaction with no competitive reduction reaction of HClO2 to form HOCl. The Chlorine
Chlorine
Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...
dioxide reacts rapidly with H2O2 to form chlorous acid
Chlorous acid
Chlorous acid is an inorganic compound with the formula HClO2. It is a weak acid. Chlorine has oxidation state +3 in this acid. The pure substance is unstable, disproportionating to hypochlorous acid and chloric acid :Although the acid is difficult to obtain in pure substance, the conjugate base,...
.
Also the formation of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
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. (See Limitation below)
Also, solid-supported reagents such as phosphate-buffered silica gel
Silica gel
Silica gel is a granular, vitreous, porous form of silica made synthetically from sodium silicate. Despite its name, silica gel is a solid. It is a naturally occurring mineral that is purified and processed into either granular or beaded form...
supported by potassium permanganate
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
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.
Scope
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. Hydroxides, epoxides, benzyl ethers, halides including iodides and even stannanes are quite stable in the reaction. 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 underdo E/Z–isomerization in the reaction.Limitations
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.Synthetic Uses
Zaragozic acidZaragozic acid
Zaragozic acids are a family of natural products produced by fungi. The first characterized zaragozic acids, A, B, and C were isolated from an unidentified sterile fungal culture, S. intermedia, and L. elatius, respectively. just outside of the European city Zaragoza, Spain on the Jalón river...
is a potent squalene synthase inhibitor
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
that can reduce the side effects caused by cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
inhibiting drugs which can also interfere with the production of important steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s. The total synthesis of Zaragozic acid applied by A. Armstrong was possible through Pinnick Oxidation. Different oxidation methods such as Jones oxidation
Jones oxidation
The Jones oxidation, is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones....
, 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.