molecules Communication Practical Synthesis of 2-Iodosobenzoic Acid (IBA) without Con- Communication taminPracticalation Synthesis by Hazardous of 2-Iodosobenzoic 2-Iodoxybenzoic Acid Acid (IBA) (IBX) without under MildContamination Conditions by Hazardous 2-Iodoxybenzoic Acid (IBX) under Mild Conditions Hideyasu China 1,2,*, Nami Kageyama 2, Hotaka Yatabe 2, Naoko Takenaga 3 and Toshifumi Dohi 2,* Hideyasu China 1,2,*, Nami Kageyama 2, Hotaka Yatabe 2, Naoko Takenaga 3 and Toshifumi Dohi 2,* 1 Department of Medical Bioscience, Nagahama Institute of Bio-Science and Technology, 1266, Tamuracho Nagahama-shi, Shiga, 526-0829, Japan 1 2 CollegeDepartment of Pharmaceutical of Medical Bioscience, Sciences, Ritsumeikan Nagahama Institute University, of Bio-Science 1-1-1 Nojihigashi, and Technology, Kusatsu, 1266,Shiga 525–8577, JapanTamuracho; [email protected] Nagahama-shi, Shiga (H.Y.), 526-0829, [email protected] Japan (N.K.) 2 3 FacultyCollege of of Pharmacy, Pharmaceutical Meijo Sciences,University, Ritsumeikan 150 Yagotoyama, University, Tempaku 1-1-1- Nojihigashi,ku, Nagoya 468 Kusatsu,-8503, ShigaJapan; 525-8577, ntakenag@Japan; [email protected] (N.K.); [email protected] (H.Y.) 3 * Correspondence:Faculty of Pharmacy, h_china@nagahama Meijo University,-i-bio.ac.jp 150 Yagotoyama, (H.C.), [email protected] Tempaku-ku, Nagoya 468-8503, (T.D.) Japan; [email protected] * Correspondence: [email protected] (H.C.); [email protected] (T.D.) Abstract: We report a convenient and practical method for the preparation of nonexplosive cyclic hypervalent iodine(III) oxidants as efficient organocatalysts and reagents for various reactions using Abstract: We report a convenient and practical method for the preparation of nonexplosive cyclic Oxone® in aqueous solution under mild conditions at room temperature. The thus obtained 2-io- hypervalent iodine(III) oxidants as efficient organocatalysts and reagents for various reactions us- dosobenzoic acids (IBAs) could be used as precursors of other cyclic organoiodine(III) derivatives ing Oxone® in aqueous solution under mild conditions at room temperature. The thus obtained by the solvolytic derivatization of the hydroxy group under mild conditions of 80 °C or lower tem- 2-iodosobenzoic acids (IBAs) could be used as precursors of other cyclic organoiodine(III) deriva- perature. These sequential procedures are highly reliable to selectively afford cyclic hypervalent◦ Citation: China, H.; Kageyama, N.; tives by the solvolytic derivatization of the hydroxy group under mild conditions of 80 C or iodine compounds in excellent yields without contamination by hazardous pentavalent iodine(III) Yatabe, H.; Takenaga, N.; Dohi, T. lower temperature. These sequential procedures are highly reliable to selectively afford cyclic hy- compound. Practical Synthesis of 2-Iodosoben- pervalent iodine compounds in excellent yields without contamination by hazardous pentavalent zoic Acid (IBA) Without Contamina- Citation: China, H.; Kageyama, N.; iodine(III) compound. ® tion by Hazardous 2-Iodoxybenzoic Keywords: cyclic organoiodine(III) compounds; Oxone ; water, solvolytic functionalization, mild Yatabe, H.; Takenaga, N.; Dohi, T. Acid (IBX) Under Mild Conditions. condition, metal-free, 2-iodosobenzoic acid ® Practical Synthesis of Keywords: cyclic organoiodine(III) compounds; Oxone ; water, solvolytic functionalization, mild Molecules 2021, 26, x. 2-Iodosobenzoic Acid (IBA) without condition, metal-free, 2-iodosobenzoic acid https://doi.org/10.3390/xxxxx Contamination by Hazardous 2-Iodoxybenzoic Acid (IBX) under Academic Editor: Maged Henary Mild Conditions. Molecules 2021, 26, 1. Introduction Received: 28 February 2021 1897. https://doi.org/10.3390/ 1. IntroductionCyclic hypervalent iodine reagents, such as 2-iodosobenzoic acid (IBA) and 2-io- Accepted: 24 March 2021 molecules26071897 doxybenzoic acid (IBX) are nonmetallic green oxidants with excellent recyclability [1–3]. Published: date Cyclic hypervalent iodine reagents, such as 2-iodosobenzoic acid (IBA) and 2-iodoxybenzoic IBAacid (IBX)and IBX are nonmetalliccan be regenerated green oxidants from 2 with-iodobenzoic excellent recyclabilityacid (2-IB) without [1–3]. IBA requ andiring IBX an can ex- be Academic Editor: Maged Henary Publisher’s Note: MDPI stays neu- ternalregenerated ligand from except 2-iodobenzoic for water acidin th (2-IB)is reoxidation without requiring step. This an externalis because ligand the exceptcarboxy for group water tral with regard to jurisdictional adjacentin this reoxidation to the iodine step. atom This isserves because as an the endogenous carboxy group ligand. adjacent Recently, to the iodineIBA, a atomrepresenta- serves Received: 28 February 2021 claims in published maps and institu- tiveas an trivalent endogenous cyclic ligand. hypervalent Recently, iodine IBA, oxidant, a representative has been trivalent used as cyclica catalyst hypervalent and reagent iodine in Accepted: 24 March 2021 tional affiliations. variousoxidant, hasreactions been used, i.e., as decarboxylative a catalyst and reagent alkynylation in various [4,5], reactions, decarboxylative i.e., decarboxylative acylarylation alkyny- Published: 27 March 2021 [6],lation oxyalkenylation [4,5], decarboxylative [7], oxyarylation acylarylation [8], [ 6oxidative], oxyalkenylation C–H arylation [7], oxyarylation [9], C–H hydroxylation [8], oxidative [C–H10], C arylation-H oxidation [9], C–H [11,12], hydroxylation ring-opening [10 ],hydrazination C-H oxidation [13 [11], ,and12], asymmetric ring-opening intramolec- hydrazina- Publisher’s Note: MDPI stays neutral ulartion [α13-cyclopropanation], and asymmetric intramolecular[14]. IBA derivativesα-cyclopropanation containing OAc [14]. [15 IBA–28 derivatives], OMe [29 containing–32], OTs with regard to jurisdictional claims in Copyright: © 2021 by the authors. 3 3 3 published maps and institutional affil- [33OAc–35 [15], –OTf28], OMe[36,37 []29, Cl–32 [38], OTs–42] [,33 F– [4335],–45 OTf], CN [36, 37[4],6] Cl, N [38 [47–42–],54 F], [ 43CF–45 [55,56], CN] [, 46OCOCF], N3 [47 [–5547]],, Licensee MDPI, Basel, Switzerland. iations. alkynylCF3 [55,56 [58],– OCOCF62] ligands3 [57], instead alkynyl of [58 the–62 hydroxy] ligands insteadgroup have of the also hydroxy found group application have also in found var- This article is an open access article iousapplication reactions in various (Figure reactions 1). (Figure1). distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licensesCopyright: © 2021 by the authors. /by/4.0/).Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Figure 1. 22-Iodosobenzoic-Iodosobenzoic acid acid ( (IBA)IBA) and and its its precursor precursor 2 2-iodobenzoic-iodobenzoic acid (2 (2-IB).-IB). Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ Although IBAs can be prepared from 2-IBs by existing methods (Figure2)[ 63–66], the 4.0/). development of a safer and more efficient method for their synthesis is highly desirable. Molecules 2021, 26, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/molecules Molecules 2021, 26, 1897. https://doi.org/10.3390/molecules26071897 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 18 Molecules 2021, 26, 1897 2 of 18 Although IBAs can be prepared from 2-IBs by existing methods (Figure 2) [63–66], the development of a safer and more efficient method for their synthesis is highly desira- bleAs. shownAs shown in Figurein Figure2, IBAs 2, IBA cans can be be further further oxidized oxidized to to pentavalent pentavalent cyclic cyclic hypervalent hypervalent IBXIBXss [ [6767]],, which which need need to to be be prevent preventeded for for the the preparation preparation of of IBAs IBAs [68 [68–70–70], mainly], mainly due due to theto the explosive explosive nature nature of IBXs of IBXs on heating on heating and impact and impact,, while while IBXs are IBXs useful are usefulin some in small some- scalesmall-scale reactions reactions [71–76] [.71 Thus,–76]. contamination Thus, contamination by IBX in by the IBX IBA in theproducts IBA products should be should avoided be foravoided long-term for long-term safe storage safe or storage large-scale or large-scale use. use. Figure 2. 2. SynthesisSynthesis of of2-iodosobenzoic 2-iodosobenzoic acids acids (IBAs (IBAs)) and and2-iodoxybenzoic 2-iodoxybenzoic acidsacids (IBXs) (IBXs) from 2 from-iodo- 2- benzoiciodobenzoic acids acids (2-IBs (2-IBs).). InIn recent recent decades, decades, many many reactions reactions using Oxone ® ,, which which is is an an inexpensive inexpensive and and com- com- mercially available stable stable triple triple salt salt (2KHSO (2KHSO55/KHSO/KHSO4/K4/K2SO2SO4), have4), have been been developed developed for practicalfor practical synthetic synthetic purposes purposes [77]. In [77 particular,]. In particular, the use the of Oxone use of® Oxone as a re®-oxidantas a re-oxidant for pen- tavalentfor pentavalent hypervalent hypervalent iodine reagents iodine reagents is drawing is drawingattention attention for catalytic for oxid catalytication oxidation reactions [78reactions–92]. The [78 –reaction92]. The systems reaction systemsfor alcohol for alcoholoxidations oxidations [78–84] [78involving–84] involving in situ ingenerated situ gen- activeerated hypervalent active hypervalent iodine(V) iodine(V) species speciesare