Iodoxybenzoic Acid IBX

The synthetic usefulness of IBX in general is significantly restricted by its low solubility in most organic solvents with the exception of DMSO. However, in several publications it has been shown that IBX can be used as effective oxidant in solvents other than DMSO [1161-1163]. More and Finney have found that primary and secondary alcohols can be oxidized into the corresponding aldehydes or ketones in excellent 

The IBX-mediated oxygenative dearomatization of phenols leading to cyclohexa-2,4- or -2,5-dienone systems is a particularly useful synthetic transformation [292]. Representative examples include the use of IBX in key oxidation steps in the total synthesis of the resveratrol-derived polyphenol natural products 

At = Ph. 4-Bu C6H4, 2-MeC6H4,3-IC6H4.4-BrC6H4.3,4-(MeO)2C6H3, 2-PhQH4,4-(4-pyridyl)C6H4, etc. 

Ar = Ph, S-EtCsftt, 3-BrC6H4,3-FC6H4,4-EtC6H4, etc. R - R = H, alkyl, cycloalkyl, etc. 

Hypervalent Iodine Reagents in Organic Synthesis 295 IBX,CH2Cl2,0 Ctort, l-1.5h N-O 

The o-iodoxybenzoic acid (37) (p. 181) commonly known as IBX was prepared for the first time more than a century ago by Hartman and Meyer by oxidation of o-iodobenzoic acid with KBrC 3.4 This compound was not explored in organic synthesis for a long time because it was wrongly supposed that its virtual lack of solubility in common organic solvents would preclude any synthetic usefulness. IBX came to the attention of the organic 

Stevenson et al. discovered that IBX can exist as two different crystalline forms with very different solubilizing kinetics and efficiency in the preparation of Dess-Martin periodinane.8 Apparently, IBX is normally obtained as a mixture of both crystalline forms in diverse proportions, depending on minor experimental details like stirring speed. Crystals with the more efficient microcrystalline morphology can be obtained by precipitating IBX from a basic aqueous solution by addition of hydrochloric acid. 

When IBX is used as a solution in DMSO, the morphology of the original crystals obviously plays no role on the oxidizing efficiency. On the other hand, IBX can be used in the oxidation of alcohols as a suspension in many organic solvents.88 Although, one would expect that in such case the morphology of IBX crystals must play an important role on the oxidizing efficiency, no such differential behaviour has been reported in the literature.883 

It has been reported that IBX behaves as an explosive similar to trinitrotoluene.9 Apparently, the tendency to explosion on impact or on heating depends very much on IBX purity,5 7 being pure samples of reagent much safer. While a wet sample of IBX can explode above 130°C,7 a pure sample explodes above 200°C.6c Very recently, it was discovered that IBX mixed with benzoic and isophthalic acids lacks any explosive property. The corresponding formulation—containing 49% of IBX, 22% of benzoic acid and 29% of isophthalic acid—has been patented as SIBX89 and it has been claimed that it is a safe alternative to IBX with the same oxidizing efficiency.88b 

Normally, IBX is dissolved in DMSO for the oxidation of alcohols and the reaction is carried out at room temperature.3 Sometimes, the addition of co-solvents causes the precipitation of IBX, resulting in a slower but still efficient oxidation that nonetheless, normally would need heating.83 In fact, IBX oxidations can be carried out using suspensions of IBX in a solvent other than DMSO, in which IBX is virtually insoluble.83,8811 A substantial acceleration can be achieved by adding a few equivalents of DMSO. 

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Lindel and co-workers had earlier achieved cyclization of intermediate 166 with 2-iodoxybenzoic acid (IBX, Dess-Martin periodinane) to give 167 (Equation 41), followed by subsequent dehydration and dihydroxylation of G(10)—C(10zz) to an advanced synthetic intermediate <2002TL3699>. 

Several organohypervalent iodine reagents have been used for the oxidation of alcohols and phenols such as iodoxybenzene, o-iodoxybenzoic acid (IBX), bis(trifluoroa-cetoxy)iodobenzene (BTI), and Dess-Martin periodinane etc. But the use of inexpensive iodobenzene diacetate (IBD) as an oxidant, however, has not been fully exploited. Most of these reactions are conducted in high boiling DMSO or toxic acetonitrile media that results in increased burden on the environment. 

Hypervalent iodine reagents have become extremely valuable tools in organic chemistry [121]. Reagents such as the Dess-Martin periodinane have received immense attention because of its efficiency and mild reaction conditions. The precursor to the Dess-Martin periodinane, o-iodoxybenzoic acid (IBX) has also be-... 

IODOXYBENZOIC ACID (IBX)//i-Bu4NBr/CH2Cl2-H20 A MILD SYSTEM FOR SELECTIVE OXIDATION OF SECONDARY ALCOHOLS... 

The kinetics of oxidation of Dess-Martin periodinane (DMP) and its iodoxybenzoic acid (IBX) precursor have been compared to explain their often different selectivities.152 A fast pre-equilibrium produces transient iodic esters, whose axial alkoxy structure for IBX was determined by 1H NMR spectroscopy, which then disproportionate in a rate-limiting maimer to product. As a result, steric effects in alcohol oxidation reflect a balance between opposing effects on equilibrium constants and rate constants for disproportionation. With 1,2-diols DMP gives spirobicyclic... 

A variety of methods have been described to solve the task in solution.16 Common oxidative agents for this transformation include various heavy-metal reagents such as chromium-or ruthenium-based oxides, pyri-dine-S03, and dimethylsulfoxide (DMSO) in combination with acetic anhydride, carbodiimide, or oxalyl chloride for activation. One of the most prominent methods for the reliable conversion of sensitive compounds is the Dess-Martin reagent or its nonacetylated equivalent, 1-hydroxy-(17/)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX). 

Recently it has been shown, that iodine(v) reagents can also be used for such transformations. An efficient regioselective method for the oxidation of phenols to ortho-quinones 40 can be achieved using 2-iodoxybenzoic acid (IBX) 7. With a subsequent reduction this proves to be a useful procedure for the synthesis of a variety of catechols 41, Scheme 20 [94]. 

Carbonyl compounds can be functionalized in the a-position under various conditions. Treatment of ketones with (diacetoxyiodo)benzene 3, iodosoben-zene 5, or 2-iodoxybenzoic acid (IBX) 7 under basic conditions provides effi-... 

Recently it was found that iodine(v) compounds like 2-iodoxybenzoic acid (IBX) 7 can be used to affect selective oxidations at carbon atoms adjacent to aromatic systems. The mechanism of this transformation is believed to proceed via a SET (Single-Electron-Transfer) process. A postulated mechanism for the oxidation of benzylic positions is outlined in Scheme 32. This oxidation is quite general and proceeds efficiently in fluorobenzene/DMSO mixtures or in DMSO at 80 °C [ 135]. Starting from compounds 70, the corresponding aldehydes 71 can be obtained easily in good yields. 

In contrast, periodinanes (i.e. iodoxo or iodine(V) reagents), preferably as the 1-hydroxy-(li-f)-benzo-l,2-iodoxol-3-one-l-oxide (2-iodoxybenzoic acid, IBX) [20, 21] or its acetylation product, the Dess-Martin reagent [22], have been widely used for oxidation of sensitive and complex alcohols. Periodinanes have not yet been prepared on a polymer support a silica-supported IBX has been reported recently [23]. 

When 125 was subjected to a two-step sequence, reductive cleavage of the 0-0 bond and subsequent oxidative dehydration, by treatment with zinc in AcOH, the allylic diol 135 and the 1,2-oxazocine 126, as minor product, were isolated. Oxidation of the diol 135 under several different reaction conditions (pyridinium chlorochromate (PCC), 2-iodoxybenzoic acid (IBX)/EtOH, IBX/DMSO, Pyr/SOj) gave 126 in high yield (68-92%), while with tetrapropylammonium perruthenate/Wmethylmorphaline Ar-oxidc (TPAP/NMO) as oxidizing agent 126 was the minor product and the a,/3-unsaturated 7-butyrolactone 136 was obtained in 68% yield (Scheme 28) <2005JOC6995>. 

Preparation of the ortho-qamont 162 from p-hydroxyacetophenone (160). This involved silylation of acetophenone, ketal protection, desilylation, and regiose-lective oxidation of phenol to o-quinone 162 using o-iodoxybenzoic acid (IBX) (Scheme 10a). 

This reaction set has been reviewed <2003S2753>. Epoxides can be cleaved oxidatively using cyclodextrins and 2-iodoxybenzoic acid (IBX) in water <2003JOC9119>. 

One example is Swern oxidation, which uses oxalyl chloride and DMSO and is particularly suitable for the selective oxidation of alcohols to aldehydes or ketones. The disadvantages of this oxidation method are the need for low temperatures, the smell of the dimethyl sulfide formed and the possible oxidation of other heteroatoms. Dess-Martin periodinane (DMP, 5) or iodoxybenzoic acid (IBX, 6) are also common oxidizing agents. The main advantage of these two methods is the short reaction time at room temperature. However, typical problems are the low solubility of IBX and the formation of byproducts. In this context, Finney et al. have reported an interesting procedure avoiding these problems by a variation of the temperature IBX is sufficiently soluble in solvents such as ethyl acetate or dichloromethane at elevated temperatures, whereas it is insoluble in these solvents at room temperature. Because of this, the remaining IBX as well as the IBX-derived byproducts can be separated from the reaction mixture by simple filtration. These reisolated IBX byproducts can then be reoxidized and reused. 

The following Swern oxidation is an inexpensive, mild and fast transformation. It provides aldehydes starting from primary alcohols in the absence of water, exclusively. Other mild oxidation methods for the formation of aldehydes are known Dess-Martin periodinane (DMP), o-iodoxybenzoic acid (IBX), chromium(III) reagents, tetramethylpiperidine 7V-oxide and sodium hypochlorite (TEMPO/NaOCl), tetrapropylammonium perruthenate and N-methylmorpholine 7V-oxide (TPAP/NMO), " and palladium(II)-catalyzed oxidations are reported. ... 

From alcohols or ketones via oxidation with o-iodoxybenzoic acid (IBX) HO... 

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