(Diacetoxyiodo)benzene: Applications in Organic Synthesis and Safety Considerations

General Description

Organic compounds of polycoordinated iodine have long been known. In 1886, Willgerodt presented the first preparation of PhIC12 from iodobenzene and IC13 in this journal. Only recently have iodine compounds in oxidation III gained synthetic and mechanistic significance, as described in numerous recent reviews. This renewed interest was initiated by the development of various new iodine(III) reagents 2a-d as well as iodate(1) salts 2e, which in most cases can conveniently be prepared in situ from common iodine(III) precursor, i.e. (diacetoxyiodo)benzene DIB[1-2].

(Diacetoxyiodo)benzene is a versatile reagent in organic synthesis. (Diacetoxyiodo)benzene efficiently oxidizes C-H bonds in benzylic acetals without costly metal catalysts, making it environmentally friendly.

Chemical property

(Diacetoxyiodo)benzene could be solute in AcOH, MeCN, CH2Cl2; in KOH or NaHCO3/MeOH it is equivalent to PhI(OH)2. It is a hypervalent iodine chemical with C6H5I(OCOCH3)2 formula. It is used as an oxidizing agent in organic chemistry.

Reaction property

(Diacetoxyiodo)benzene could be used in the transannular carbocyclization, vic-diazide formation, α-hydroxy dimethyl acetal formation, oxetane formation, chromone, flavone, chalcone oxidation, arene–Cr(CO)3 functionalization, phenolic oxidation and coupling, lactol fragmentation, iodonium ylides and intramolecular cyclopropanation, oxidation of amines and indoles, hydrazine derivatives (diimide and azodicarbonyls) and radical type intramolecular oxide formation.

1,2-Additions to Olefines

DIB can be used to promote 1,2 addition reactions to olefines. However, DIB is only able to transfer acetoxy groups to highly nucleophilic alkenes and cyclopentadiene; isolated double bonds are inactive under mild conditions. Over the last years various procedures have been developed, where DIB is used to activate other heteroatom containing reagents, which then add to olefinic double bonds. Triisopropylsilyl enol ethers are ideally suited for bisazidonation under radical conditions[3].

a-Functionalization of Ketones

Iodine(III) oxidation of enolizable ketones using DIB in methanolic KOH provides one of the best methods to oxidise ketones. It is generally accepted that it acts as the active intermediate. After coupling with the enolate anion, a cascade of reactions is initiated, which eventually leads to ahydroxydimethylketals. Intramolecular variants of this process have been used for constructing steroidal oxetanes from the corresponding 17-hydroxy- 17- acetyl precursors. In a few cases, DIB has been employed in the a-acetoxylation of ketones.

Allylic Oxidation of Olefines

In recent years, the iodine(III)-promoted allylic oxidation of electron-rich olefinic double bonds, particularly of carbohydrate-derived glycals and triisopropylsilyl enol ethers, have been studied in detail. This type of conversion reveals a unique reactivity pattern of polycoordinated iodine compounds and is assumed to proceed via an ionic addition/ elimination mechanism. In these examples, DIB was used for in situ generation of iodine(III)-reagents 2c and 2d. These were employed for azide transfer onto the allylic position (equ. 7 and 8) or for the allylic oxidative deblocking of glycals.

intramolecular halocyclization of unfunctionalized olefins

(Diacetoxyiodo)benzene (PIDA) was very effective for haloamidation, haloetherification, and halolactonization of unfunctionalized olefins. In the presence of 1.1 equiv of PIDA and suitable halogen sources, a variety of unfunctionalized olefins could be converted to the corresponding 1,2- bifunctional cyclic skeletons in good to excellent isolated yields, and critical intermediates for biologically interesting compounds could be obtained in high yields under mild conditions via nucleophilic substitution of the thus obtained halocyclization products.

Safety

(Diacetoxyiodo)Benzene is a chemical compound that requires careful handling due to several associated health risks. This compound is harmful if swallowed, meaning it can cause significant internal damage upon ingestion. It is also harmful when in contact with the skin, as it can penetrate the skin barrier, leading to potential systemic effects. In addition, (diacetoxyiodo)benzene causes skin irritation, which can manifest as redness, itching, or dermatitis. This compound also poses risks to eye health, as it causes serious eye irritation that could result in pain, blurred vision, or eye damage. Inhaling (diacetoxyiodo)benzene may cause respiratory irritation, indicating potential harm to the lungs and airways. These risks necessitate strict safety measures, including the use of appropriate personal protective equipment (PPE) such as gloves, safety goggles, and respirators when handling (diacetoxyiodo)benzene. Proper ventilation in work areas is also critical to mitigate inhalation risks.

Reference

1. Aman H, Wang YH, Chuang GJ. (Diacetoxyiodo)benzene-Mediated C-H Oxidation of Benzylic Acetals. ACS Omega. 2019; 5(1): 918-925.

2. Liu GQ, Li YM. Regioselective (diacetoxyiodo)benzene-promoted halocyclization of unfunctionalized olefins. J Org Chem. 2014; 79(21): 10094-10109.

3. (Diacetoxyiodo)benzene. National Center for Biotechnology Information. 2024; PubChem Compound Summary for CID 76724.

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