2-Iodoxybenzoic acid
Encyclopedia
IBX acid or 2-iodoxybenzoic acid is an organic compound
used in organic synthesis
as an oxidizing agent
. This Periodinane
is especially suited to oxidize alcohol
s to aldehyde
s. The IBX acid is prepared from 2-iodobenzoic acid, potassium bromate
and sulfuric acid
. Frigerio and co-workers have also demonstrated, in 1999 that potassium bromate may be replaced by commercially available Oxone. One of the main drawbacks of IBX is its limited solubility; IBX is insoluble in many common organic solvents. In the past, it was believed that IBX was shock sensitive
, but it was later proposed that samples of IBX were shock sensitive due to the residual potassium bromate left from its preparation. Commercial IBX is stabilized by carboxylic acid
s such as benzoic acid
and isophthalic acid
.
for an oxidation of an alcohol
to an aldehyde
according the so-called hypervalent twisting mechanism involves a ligand exchange reaction replacing the hydroxyl group by the alcohol followed by a twist and a elimination reaction
. The twist is a requirement because the iodine to oxygen double bond
is oriented out of plane with the alkoxy group and the concerted
elimination would not be able to take place. This twist reaction is a rearrangement in which the oxygen atom is moved into a proper plane for a 5 membered cyclic transition state
in the elimination reaction and is calculated by Computational chemistry
to be the rate-determining step
in the oxidation. The twist mechanism also explains why oxidation is faster for larger alcohols than for small alcohols. The twist is driven forward by the steric hindrance that exists between the ortho hydrogen atom and the protons from the alkoxy group and larger alkoxy groups create larger steric repulsion. The same computation predicts a much faster reacting IBX derivative with a 100 fold reaction rate
when this ortho hydrogen atom is replaced by a methyl group thus facilitating the twist until the elimination reaction takes prevalence as the rate determining step.
IBX exists as two tautomer
s one of which is the carboxylic acid
. The acidity of IBX which has been determined in water (pKa
2.4) and DMSO
(pKa 6.65) is known to affect organic reactions, for instance acid-catalyzed isomerization accompanying oxidations.
or polystyrene
bound IBX. In many application IBX acid is replaced by Dess-Martin periodinane
which is more soluble in common organic solvents. A sample reaction is a IBX oxidation used in the total synthesis
of eicosanoid
:
.
In 2001, K.C. Nicolaou
and co-workers published a series of papers in the Journal of the American Chemical Society
demonstrating, among other transformations, the use of IBX to oxidize benzylic carbons to conjugated aromatic carbonyl compounds.
The reaction mechanism for this glycol cleavage
is based on initial formation of an adduct between 10-I-4 IBX and DMSO to an 12-I-5 intermediate 3 in which DMSO acts as a leaving group
for incoming alcohol
4 to intermediate 5. One equivalent of water is split off forming 12-I-5 spirobicyclic periodinane 6 setting the stage for fragmentation to 7. With hydroxyl alpha protons presents oxidation to the acyloin
competes. Trifluoroacetic acid
is found to facilitate the overall reaction.
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
used in organic synthesis
Organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
as an oxidizing agent
Oxidizing agent
An oxidizing agent can be defined as a substance that removes electrons from another reactant in a redox chemical reaction...
. This Periodinane
Periodinane
Periodinanes are chemical compounds containing hypervalent iodine. These iodine compounds are hypervalent because the iodine atom in it contains more than the 8 electrons in the valence shell required for the octet rule...
is especially suited to oxidize alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s to aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s. The IBX acid is prepared from 2-iodobenzoic acid, potassium bromate
Potassium bromate
Potassium bromate , is a bromate of potassium and takes the form of white crystals or powder.-Uses in baking:Potassium bromate is typically used as a flour improver , strengthening the dough and allowing higher rising. It is an oxidizing agent, and under the right conditions, will be completely...
and sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
. Frigerio and co-workers have also demonstrated, in 1999 that potassium bromate may be replaced by commercially available Oxone. One of the main drawbacks of IBX is its limited solubility; IBX is insoluble in many common organic solvents. In the past, it was believed that IBX was shock sensitive
Shock sensitivity
Shock sensitivity is a comparative measure of the sensitivity to sudden compression of an explosive chemical compound. Determination of the shock sensitivity of a material intended for practical use is one important aspect of safety testing of explosives...
, but it was later proposed that samples of IBX were shock sensitive due to the residual potassium bromate left from its preparation. Commercial IBX is stabilized by 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...
s such as benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
and isophthalic acid
Isophthalic acid
Isophthalic acid is an organic compound with the formula C6H42. This colourless solid is an isomer of phthalic acid and terephthalic acid. These aromatic dicarboxylic acids are used as precursors to commercially important polymers, e.g. the fire-resistant material Nomex...
.
Reaction mechanism
The 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...
for an oxidation of an alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
to an aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
according the so-called hypervalent twisting mechanism involves a ligand exchange reaction replacing the hydroxyl group by the alcohol followed by a twist and a elimination reaction
Elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...
. The twist is a requirement because the iodine to oxygen double bond
Double bond
A double bond in chemistry is a chemical bond between two chemical elements involving four bonding electrons instead of the usual two. The most common double bond, that between two carbon atoms, can be found in alkenes. Many types of double bonds between two different elements exist, for example in...
is oriented out of plane with the alkoxy group and the concerted
Concerted reaction
In chemistry, a concerted reaction is a chemical reaction in which all bond breaking and bond making occurs in a single step. Reactive intermediates or other unstable high energy intermediates are not involved. Concerted reaction rates tend not to depend on solvent polarity ruling out large buildup...
elimination would not be able to take place. This twist reaction is a rearrangement in which the oxygen atom is moved into a proper plane for a 5 membered cyclic transition state
Transition state
The transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest energy along this reaction coordinate. At this point, assuming a perfectly irreversible reaction, colliding reactant molecules will always...
in the elimination reaction and is calculated by Computational chemistry
Computational chemistry
Computational chemistry is a branch of chemistry that uses principles of computer science to assist in solving chemical problems. It uses the results of theoretical chemistry, incorporated into efficient computer programs, to calculate the structures and properties of molecules and solids...
to be the rate-determining step
Rate-determining step
The rate-determining step is a chemistry term for the slowest step in a chemical reaction. The rate-determining step is often compared to the neck of a funnel; the rate at which water flows through the funnel is determined by the width of the neck, not by the speed at which water is poured in. In...
in the oxidation. The twist mechanism also explains why oxidation is faster for larger alcohols than for small alcohols. The twist is driven forward by the steric hindrance that exists between the ortho hydrogen atom and the protons from the alkoxy group and larger alkoxy groups create larger steric repulsion. The same computation predicts a much faster reacting IBX derivative with a 100 fold reaction rate
Reaction rate
The reaction rate or speed of reaction for a reactant or product in a particular reaction is intuitively defined as how fast or slow a reaction takes place...
when this ortho hydrogen atom is replaced by a methyl group thus facilitating the twist until the elimination reaction takes prevalence as the rate determining step.
IBX exists as two tautomer
Tautomer
Tautomers are isomers of organic compounds that readily interconvert by a chemical reaction called tautomerization. This reaction commonly results in the formal migration of a hydrogen atom or proton, accompanied by a switch of a single bond and adjacent double bond...
s one of which is the 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...
. The acidity of IBX which has been determined in water (pKa
PKA
PKA, pKa, or other similar variations may stand for:* pKa, the symbol for the acid dissociation constant at logarithmic scale* Protein kinase A, a class of cAMP-dependent enzymes* Pi Kappa Alpha, the North-American social fraternity...
2.4) and DMSO
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
(pKa 6.65) is known to affect organic reactions, for instance acid-catalyzed isomerization accompanying oxidations.
Scope
IBX is also available as silica gelSilica 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...
or polystyrene
Polystyrene
Polystyrene ) also known as Thermocole, abbreviated following ISO Standard PS, is an aromatic polymer made from the monomer styrene, a liquid hydrocarbon that is manufactured from petroleum by the chemical industry...
bound IBX. In many application IBX acid is replaced by Dess-Martin periodinane
Dess-Martin periodinane
Dess–Martin periodinane is a chemical reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. This periodinane has several advantages over chromium- and DMSO-based oxidants that include milder conditions , shorter reaction times, higher yields, simplified workups,...
which is more soluble in common organic solvents. A sample reaction is a IBX oxidation used in the total synthesis
Total synthesis
In organic chemistry, a total synthesis is, in principle, the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes. In practice, these simpler pieces are commercially available in bulk and semi-bulk quantities, and are often...
of eicosanoid
Eicosanoid
In biochemistry, eicosanoids are signaling molecules made by oxidation of twenty-carbon essential fatty acids, ....
:
.
In 2001, K.C. Nicolaou
Kyriacos Costa Nicolaou
Kyriacos Costa Nicolaou is a Cypriot-American chemist known for the total synthesis of natural products.-Biography:K. C. Nicolaou was born on July 5, 1946, in Karavas, Cyprus where he grew up and went to school until the age of 18. In 1964, he went to England where he spent two years learning...
and co-workers published a series of papers in the Journal of the American Chemical Society
Journal of the American Chemical Society
The Journal of the American Chemical Society is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the Journal of Analytical and Applied Chemistry and the American Chemical Journal...
demonstrating, among other transformations, the use of IBX to oxidize benzylic carbons to conjugated aromatic carbonyl compounds.
Oxidative cleavage
IBX is notable for oxidizing vicinal diols (or glycols) to diketones without cleavage of the carbon-carbon bond, but oxidative cleavage of glycols to dialdehydes or diketones can occur when modified conditions are used (elevated temperatures or trifluoroacetic acid solvent).The reaction mechanism for this glycol cleavage
Glycol cleavage
Glycol cleavage is a specific type of organic chemistry oxidation. The carbon–carbon bond in a Glycol cleavage is a specific type of organic chemistry oxidation. The carbon–carbon bond in a Glycol cleavage is a specific type of organic chemistry oxidation. The carbon–carbon bond in a (vicinal diol...
is based on initial formation of an adduct between 10-I-4 IBX and DMSO to an 12-I-5 intermediate 3 in which DMSO acts as a leaving group
Leaving group
In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...
for incoming alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
4 to intermediate 5. One equivalent of water is split off forming 12-I-5 spirobicyclic periodinane 6 setting the stage for fragmentation to 7. With hydroxyl alpha protons presents oxidation to the acyloin
Acyloin
Acyloins are a class of organic compounds in organic chemistry sharing a common functional group consisting of a hydroxyl group placed on the α-position of a carbonyl group.- Nomenclature :Common types of ketols include:...
competes. Trifluoroacetic acid
Trifluoroacetic acid
Trifluoroacetic acid is the simplest stable perfluorinated carboxylic acid chemical compound, with the formula CF3CO2H. It is a strong carboxylic acid due to the influence of the electronegative trifluoromethyl group. TFA is almost 100,000-fold more acidic than acetic acid...
is found to facilitate the overall reaction.