Iodoxybenzoic acid

Alternate Name o-iodoxybenzoic acid l-hydroxy-l,2-benziodo-xol-3(17/)-one-1-oxide, IBX. 

Solubility soluble in DMSO, DMSO/THF mixtures insoluble in H2O and most organic solvents. 

Preparative Methods not commercially available. IBX was first synthesized in 1893, and is the penultimate precursor of the Dess-Martin periodinane reagent. IBX is prepared by the slow addition (0.5 h) of potassium bromate (76.0 g, 0.45 mol) to a rapidly stirred sulfuric acid mixture (0.73 M, 730 mL) containing 2-iodobenzoic acid (85.2 g, 0.34 mol). The reaction temperature is maintained below 55 °C until addition is complete. The reaction mixture is heated to 65 °C for 3.6 h. The flask is cooled to 0 °C, and the solid is filtered and washed with water (1000 mL) and ethanol (2 x 50 mL) to afford IBX in 93-98% yield. An additional ether wash (3 x 50 mL) is beneficial. Other oxidants such as potassium permanganate, chlorine, or oxone can also be employed. 

Handling, Storage, and Precaution moisture stable, explosive under excessive heating ( 200 °C) or impact.  

Oxidation of Alcohols to Aldehydes and Ketones. Hyper-valent iodine compounds have powerful oxidizing capabilities. However, IBX possesses different properties than many similar oxidants, such as the related analogs iodoxybenzene and m-iodoxybenzoic acid. Until recently, the major application of IBX was its use in DMSO for the oxidation of primary alcohols to aldehydes at room temperature, without the danger of over-oxidation to carboxylic acids. The related iodo-oxy reagents oxidize benzyl alcohols to benzaldehydes at elevated temperatures in benzene (80 °C, 5-10 h) or in acetic acid (rt, 24 h), while IBX oxidizes the same compounds in 15 min (or less) at room temperature. IBX is equally effective for the oxidation of secondary alcohols to ketones under analogous conditions. Even sterically hindered alcohols are readily oxidized. Bomeol undergoes smooth oxida- 

---

Horner-Wadsworth-Emmons or Horner-Wittig-Emmons 2-iodoxybenzoic acid... 

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>. 

IoDOXYBENZOIC acid (mXyn-BuiNBr/CHaCL-HaO A MILD SYSTEM FOR SELECTIVE... 

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

Iodoxybenzoic acid. Potassium bromate (76.0 g, 0.45 mol) is added over a half-an-hour period to a vigorously stirred mixture of o-iodobenzoic acid (85.2 g, 0.34 mol) and 730 ml of 0.73 m sulphuric acid. During the addition the reaction mixture is kept below 55 °C. The mixture is warmed to 65 °C and stirred for 3.6 hours. Cooling to 0°C, filtering, and washing with 1000 ml of water and two 50-ml portions of ethanol give the product (89.1 g, 93%). 

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). 

Tetrahydroquinoline-2-methanoles 184 were obtained from the diaste-reomeric mixtures of cyclic hemiacetals 183 by treatment with aqueous solution of NaOH in THF (08T2321). C4b S) epimers of 183 (R = Me, Ph) furnished the entiomers of 184 (R = Me, Ph) in 84-90% yields. The oxidation of cyclic hemiacetals 183 with 2-iodoxybenzoic acid afforded 1-for-myltetrahydroquinoline-2-aldehydes 185. Enantiomers of 185 (R = Me, Ph, C=CPh) were prepared similarly. 

Scheme 5. Polymer bound 2-iodoxybenzoic acid reagents...

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]. 

The formation of the products 43 and 45 has also been studied from a mechanistic point of view. Labeling studies with H2180 revealed that two molecules of acetyl-2-iodoxybenzoic acid (formed by the reaction between Dess-Martin Peri-odinane 8 and water) are involved in para-quinone formation. It is suspected that the substituent in 2-position in 42 blocks another molecule of acetyl-2-iodoxybenzoic acid attacking the initially formed product leading to the formation of ortho-imidoquinones. Anilides substituted in the 3-position does lead to complex mixtures in the oxidation reaction. 

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. 

Oxidation of thiochroman-4-ol to thiochroman-4-one can be achieved without competing Pummerer rearrangement using triphenylphosphine dihalides in DMSO (Equation 92) <2002TL8355>. This oxidation has also been achieved using polymer-bound periodinane (82% yield) <1999T6785> and 2-iodoxybenzoic acid is also effective (92%) <1995JOC7272>. 

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>. 

Indoles and azaindoles undergo smooth oxidation with 2-iodoxybenzoic acid in the presence of indium(lll) chloride (aqueous media, 80 °C) to afford the corresponding isatins in excellent yields <2007S0693>. A peculiar rearrangement to 3//-benzo[< ]indole during the NiS-catalyzed dehydrogenation of 4,5-dihydro-l//-benzo g]indole (350 °C) was reported <2007MC296>. 

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

The phenolic ring in estrone can be readily oxidized. Reaction of estrone with Fremy salts (peroxylamine disulfonate) affords a mixture of the two isomeric catechols. In a more controlled manner, treatment of estrone with 2-iodoxybenzoic acid (22-1) leads intially to a mixture of the 2,3-quinone (22-2) and its 3,4-isomer (22-3) (Scheme 3.22). These products are then reduced in situ with ascorbic acid to afford 2-hydroxyestrone (22-4) and 4-hydroxyestrone (22-5). 

---