ORIENTAL JOURNAL OF CHEMISTRY ISSN: 0970-020 X CODEN: OJCHEG An International Open Access, Peer Reviewed Research Journal 2020, Vol. 36, No.(5): Pg. 792-803 www.orientjchem.org 2-Iodoxybenzoic Acid: An Oxidant for Functional Group Transformations: (A-Review) VIPIN A. NAIR Department of chemistry, REVA University, Yelahanka, Bangalore 560064, India. *Corresponding author E-mail: [email protected] http://dx.doi.org/10.13005/ojc/360501 (Received: August 28, 2020; Accepted: September 29, 2020) ABstract A major application of 2-Iodoxybenzoic acid (IBX) is the oxidation of alcohols to carbonyl compounds, at room temperature. IBX is insoluble in almost all solvents, except DMSO. IBX tolerates amine functionality and is therefore used for the oxidation of amino alcohols to amino carbonyl compounds. IBX oxidizes 1,2-glycols without the cleavage of the glycol carbon-carbon bond. Allylic and benzylic positions are also susceptible to oxidation by IBX. Synthesis of a,b-unsaturated carbonyl compounds from carbonyl compounds can be accomplished by using IBX as oxidant. Silyl enol ethers undergo oxidation upon exposure to IBX and 4-methoxypyridine N-oxide. Water-soluble derivatives of IBX, and polymer-based IBX, with additional advantages, have also been developed. IBX mediated transformations facilitate the construction of diverse heterocyclic systems. Keywords: 2-Iodoxybenzoic acid, Oxidation, Alcohols, Carbonyl compounds, Single electron transfer. IntroDUCTION useful oxidants in organic synthesis. O OH AcO OAc 2-Iodoxybenzoic acid (IBX), a hypervalent I I OAc iodine(V) reagent (Fig. 1) finds numerous applications O O as an oxidant. It is effective in carrying out oxidation O O of alcohols, benzylic and allylic sites, and carbon centres adjacent to carbonyl functionalities. 2-Iodoxybenzoic acid (IBX) Dess-Martin Periodinane (DMP) Inferences drawn from studies indicate that some Fig. 1. Hypervalent Iodine reagents of these reactions proceed by single electron 2-Iodoxybenzoic acid (IBX) is known transfer (SET) mechanism. Electron transfer from for several decades, but its utility was limited by the substrate to IBX forms a radical cation, which insolubility in most organic solvents, except DMSO. is converted to product. Detailed investigations on IBX is easily prepared from 2-iodobenzoic acid by an multifunctional substrates would allow to decipher oxidation reaction. Oxone (2KHSO5-KHSO4-K2SO4) the chemo- and regioselectivity of the reactions. is widely employed as an oxidant in the preparation The reagent has the potential to be one of the highly of IBX.1 The oxidation is performed at 70°C in water This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC- BY). Published by Oriental Scientific Publishing Company © 2018 NAIR., Orient. J. Chem., Vol. 36(5), 792-803 (2020) 793 (Fig. 2). IBX is crystallized out of the reaction mixture OH O in high yields and good purity, by cooling. Use of NR NR excess of oxone reduces the reaction time. The 2 IBX 2 procedure is environment friendly, with the sulfate salts as the only by products. DMSO, TFA Scheme 2. Oxidation of amino alcohols O OH Carboxylic acids and esters remain intact in I I Oxone (1.3 equiv.) presence of IBX, while phenols are unstable (Table O H2O, 70°C, 3h 1, Entry 4). At room temperature, phenols undergo CO2H double oxidation (Scheme 3) to afford o-quinones.4 O IBX However, phenols with electron withdrawing groups are not oxidised. Fig. 2. Preparation of IBX using Oxone IBX has been used to convert alcohols and O O 1,2-diols to carbonyl compounds (Scheme 1). The OH IBX transformation occurs without over-oxidation (Table DMF X X 1, Entries 1,2) to carboxylic acids.2 IBX does not Y Y require an inert atmosphere for the reaction. X, Y - Electron donating groups Scheme 3. Oxidation of phenols OH IBX O 2 1,4-Diols are oxidised to g-lactols (Table 1, 1 R DMSO, RT 2 R R1 R Entry 5) in good yields.5 No over-oxidation to lactones was observed. For instance, the diol prepared OH OH IBX OH O O O by hydroboration of (1S)-isopulegol afforded a or R R diastereomeric mixture of lactols (Scheme 4). DMSO, RT R R R R Scheme 1. Oxidation of alcohols and 1,2-diols CH3 CH3 Alcohols can be selectively oxidised in the IBX presence of amines (Table 1, Entry 3). Thus IBX converts amino alcohols to amino carbonyl compounds OH DMSO O OH (Scheme 2). Amines are usually protonated in situ with H3C H3C OH an acid (TFA), during the reaction.3 Scheme 4. Oxidation of 1,4-diols Table 1: IBX mediated functional group transformations Entry Substrate Product Conditions Yield H 1 OH IBX (1.0 equiv.), 97% O DMSO, RT OH O 2 IBX (2.5 equiv.), 81% DMSO, RT OH O OH O 3 IBX (1.1 equiv.), 89% NH2 NH2 TFA (1.1 equiv.), DMSO, RT O OH O 4 IBX (1.0 equiv.), 99% MeO MeO DMF, 25°C H H OH OH H 5 O IBX (1.2 equiv.), 88% OH DMSO, 23°C H H OH CHO 6 aM-IBX (2.0 equiv.), 90% H2O, RT NAIR., Orient. J. Chem., Vol. 36(5), 792-803 (2020) 794 OH CHO 7 bP-IBX (1.2 equiv.), 97% MeO MeO THF, RT OTMS O 8 cIBX-MPO (1.5 equiv.), 90% DMSO, -10°C to 25°C 9 CHO IBX (1.0 equiv.), 96% OH d b-CD (0.1 equiv.), H2O, RT CH3 CHO 10 IBX (3.0 equiv.), 85% PhF:DMSO (2:1), 85°C aModified IBX (Water soluble derivative); bPolymer supported IBX; cIBX-Methoxy Pyridine N-oxide; db-Cyclodextrin A water-soluble derivative of IBX was A complex of IBX and 4-methoxypyridine developed for oxidizing alcohols. The synthesis was N-oxide (MPO) (Scheme 6) converts carbonyl achieved by the conversion of 3-nitrophthalic acid to compounds and trimethyl silyl enol ethers into 3-iodophthalic acid (Fig. 3) and subsequent oxidation corresponding a,b-unsaturated carbonyl compounds.8 using KBrO .6 This derivative of IBX oxidises allylic and 3 Reactive groups such as amines, sulfides and benzylic alcohols in water (Scheme 5). Over-oxidation products were not observed (Table 1, Entry 6). mesylates were unaffected. The enolate formed by NO the conjugate addition of a cuprate reagent (RMgX, 2 NO2 H , Pd-C NH2 SOCl2, heat 2 NaNO2, HCl CH OH, heat CH3OH KI CuBr.SMe ) to an enone was trapped as the silyl enol CO2H 3 CO2CH3 CO2CH3 2 CO2H CO2CH3 CO2CH3 ether. Subsequent oxidation of the silyl enol ether O OH regenerated a b-substituted enone (Table 1, Entry 8). I I I NaOH, THF–H2O KBrO3 O aq. HCl H2SO4 O OTMS O CO2CH3 CO2H CO CH CO H CO H O 2 3 2 2 MgX CuBr.SMe2 IBX-MPO Fig. 3. Preparation of water-soluble derivative of IBX TMEDA, TMSCl, THF DMSO HO O -78°C to 25°C I O H Scheme 6. Conversion of silyl enol ethers to enones O OH CO2H O H2O, RT The dehydrogenation reactions of carbonyl HO O I compounds proceed through enolization facilitated O H CO H O by IBX. This is followed by a single electron OH 2 O H2O, 60°C transfer to IBX. The resulting radical cation affords Scheme 5. Oxidation of allylic and benzylic alcohols a,b-unsaturated carbonyl compound (Fig. 5). It is 2-Amino-5-hydroxybenzoic acid was assumed that the silyl enol ethers also undergo a transformed to the tert-butyl ester of 2-iodo-5- hydroxy benzoic acid (Fig. 4). The phenolic hydroxy similar oxidation with IBX. MeO MeO MeO group was subsequently coupled to aminopropylsilica O O O MeO O gel with acetyl group as the linker. Cleavage of the N O N O N O O N tert-butyl ester and oxidation with oxone afforded O I O I O I I O O O O HO 7 O O O the polymer-supported IBX reagent. Primary and O R1 R1 R1 secondary alcohols were oxidized by this reagent, in H 1 2 R R2 R2 R THF medium (Table 1, Entry 7). This reagent offers R2 the advantages of polymer-support and the oxidant. Fig. 5. Formation of a,b-unsaturated carbonyl compounds The reduced reagent was separated by filtration, and b-Cyclodextrin catalyses the oxidation of regenerated by oxidation. alcohols and diols, with IBX. Water-acetone mixture OH OH OH N,N-dimethyl formamide 9 NaNO , H SO di-tert-butyl acetal 2 2 4 1.NaH, BrCH2COOEt was employed as the solvent. Cyclodextrin exerts COOH KI COOH CO2tBu 2. NaOH NH2 I I catalytic effect through non-covalent interactions. H H N SiO2 N SiO O COOH O O 2 Aryl carbinols (Table 1, Entry 9) gave better yields aminopropylsilica gel O 1. TFA O than the aliphatic alcohols. Selectivity was observed DIC, HOBt 2. Oxone CO2tBu CO2tBu O I I HO I O with vicinal diols, oxidizing only the secondary O Fig. 4. Preparation of polymer supported IBX hydroxy group a to the benzene ring (Scheme 7). NAIR., Orient. J. Chem., Vol. 36(5), 792-803 (2020) 795 OH O OH IBX cat. 2-Iodoxy benzoic acid/Oxone OH OH or 1 O b-Cyclodextrin cat. 2-Iodoso benzoic acid/Oxone R Water-Acetone, RT R1 OH Scheme 7. b-cyclodextrin catalysed oxidation of benzyl alcohol MeCN-H2O Oxidation of benzylic positions (Table 1, R2 Entry 10) occurs efficiently with IBX in DMSO at 80- R2 90°C.10 Over-oxidation products were not observed R1 O 1 OH even in the case of electron-rich substrates. R Tetrahydronaphthalenes yielded the corresponding Scheme 11.