2-Iodoxybenzoic acid (IBX) is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...

used in organic synthesis as an

oxidizing agent An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxi ...

. This periodinane is especially suited to

oxidize Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

alcohols to

aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

s. IBX is prepared from 2-iodobenzoic acid,

potassium bromate Potassium bromate (KBrO3), is a bromate of potassium and takes the form of white crystals or powder. It is a strong oxidizing agent. It is a toxic and carcinogenic compound. Preparation Potassium bromate is produced when bromine is passed throug ...

, and sulfuric acid. Frigerio and co-workers have also demonstrated, in 1999 that potassium bromate may be replaced by commercially available

Oxone Potassium peroxymonosulfate is widely used as an oxidizing agent. It is the potassium salt of peroxymonosulfuric acid. Usually potassium peroxymonosulfate refers to the triple salt known as oxone. The standard electrode potential for potassium ...

. 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 acids such as

benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, ...

and

isophthalic acid Isophthalic acid is an organic compound with the formula C6H4(CO2H)2. This colorless solid is an isomer of phthalic acid and terephthalic acid. The main industrial uses of purified isophthalic acid (PIA) are for the production of polyethylene te ...

Reaction mechanism

The reaction mechanism for an oxidation of an alcohol to an

according to the hypervalent twisting mechanism involves a ligand exchange reaction replacing the hydroxyl group by the alcohol followed by a twist and an

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 one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 r ...

. The twist is a requirement because the iodine to oxygen

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betwee ...

is oriented out of plane with the

alkoxy In chemistry, the alkoxy group is an alkyl group which is singularly bonded to oxygen; thus . The range of alkoxy groups is vast, the simplest being methoxy (). An ethoxy group () is found in the organic compound ethyl phenyl ether (, also ...

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 chemistry, 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 potential energy along this reaction coordinate. It is often marked ...

in the elimination reaction and is calculated by Computational chemistry to be the

rate-determining step In chemical kinetics, the overall rate of a reaction is often approximately determined by the slowest step, known as the rate-determining step (RDS or RD-step or r/d step) or rate-limiting step. For a given reaction mechanism, the prediction of the ...

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 Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivity of ions ...

that exists between the ortho hydrogen atom and the protons from the

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 Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hyd ...

s one of which is the carboxylic acid. The

acidity In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a ...

of IBX which has been determined in water ( pKa 2.4) and

DMSO Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula ( CH3)2. This colorless liquid is the sulfoxide most widely used commercially. It is an important polar aprotic solvent that dissolves both polar and nonpolar compounds ...

(pKa 6.65) is known to affect organic reactions, for instance acid-catalyzed

isomerization In chemistry, isomerization or isomerisation is the process in which a molecule, polyatomic ion or molecular fragment is transformed into an isomer with a different chemical structure. Enolization is an example of isomerization, as is tautomeriz ...

accompanying oxidations.

Scope

IBX is also available as

silica gel Silica gel is an amorphous and porous form of silicon dioxide (silica), consisting of an irregular tridimensional framework of alternating silicon and oxygen atoms with nanometer-scale voids and pores. The voids may contain water or some other l ...

or polystyrene bound IBX. In many applications, IBX is replaced by Dess–Martin periodinane which is more soluble in common organic solvents. A sample reaction is an IBX oxidation used in the

total synthesis Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially-available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes i ...

eicosanoid Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a s ...

: More and Finney and Van Arman have demonstrated that common organic solvents are suitable for many IBX oxidations, despite its low solubility, and in fact may simplify product purification. : In 2001, K. C. Nicolaou and co-workers published a series of papers in the ''

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 Analytic ...

'' demonstrating, among other transformations, the use of IBX to oxidize primary and secondary benzylic carbons to aromatic aldehydes and ketones, respectively.

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 two aldehydes or ketones can occur when modified conditions are used (elevated temperatures or trifluoroacetic acid solvent). : The reaction mechanism for this glycol cleavage is based on initial formation of an adduct between 10-I-4 IBX and DMSO to a 12-I-5 intermediate 3 in which DMSO acts as a

leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited ...

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 present, oxidation to the

acyloin Acyloins or α-hydroxy ketones are a class of organic compounds which all possess a hydroxy group adjacent to a ketone group. The name acyloin is derived from the fact that they are formally derived from reductive coupling of carboxylic acyl grou ...

competes.

Trifluoroacetic acid Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with ...

is found to facilitate the overall reaction. :

α-Hydroxylations

Kirsch and co-workers were able to hydroxylate keto compounds with IBX in α-position under mild conditions. This method could be extended to β-keto esters.

Oxidation of β-hydroxyketones to β-diketones

Bartlett and Beaudry discovered that IBX is a valuable reagent for the transformation of β-hydroxyketones to β-diketones. IBX provides yields superior to both the Swern and Dess–Martin oxidation protocols.

References

{{DEFAULTSORT:Iodoxybenzoic acid, 2- Iodates Periodinanes Iodine heterocycles Oxygen heterocycles Reagents for organic chemistry Oxidizing agents Heterocyclic compounds with 2 rings