1362 Korean J. Chem. Eng., 31(8), 1362-1367 (2014) DOI: 10.1007/s11814-014-0036-0 INVITED REVIEW PAPER pISSN: 0256-1115 eISSN: 1975-7220 INVITED REVIEW PAPER † To whom correspondence should be addressed. E-mail: wjc0828@gmail.com ‡ The authors contributed equally in this work. Copyright by The Korean Institute of Chemical Engineers. Metal-free mild oxidation of 5-hydroxymethylfurfural to 2,5-diformylfuran Neha Mittal ‡ , Grace M. Nisola ‡ , Lenny B. Malihan, Jeong Gil Seo, Seong-Poong Lee, and Wook-Jin Chung † Energy and Environment Fusion Technology Center (E 2 FTC), Department of Energy and Biotechnology (DEB), Myongji University, Myongji-ro 116, Nam-dong, Cheoin-gu, Yongin City, Gyeonggi-do 449-728, Korea (Received 27 September 2013 • accepted 28 January 2014) Abstract-The potential of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-hydroxy-TEMPO radical) as an oxidant with [bis(acetoxy)-iodo]benzene (BAIB) and acetic acid (CH 3 COOH) as co-oxidants to convert 5-hydroxymethylfur- fural (5-HMF) into 2,5-diformylfuran (2,5-DFF) was investigated. The effects of oxidant/acid dosages, choice of ap- propriate solvent, reaction temperature and time were determined to maximize the 2,5-DFF yield. Optimally, 66% 2,5- DFF yield was achieved in TEMPO/BAIB/CH 3 COOH system at 30 o C after 45 min in ethyl acetate. The reaction system is environmentally benign (metal-free) and energy efficient (mild at short reaction period). With scarce reports on 2,5- DFF production, the developed system provides an alternative route for a better access and wider application of this important platform chemical. Keywords: 2,5-Diformylfuran, 5-Hydroxymethylfurfural, Homogeneous, Oxidation, Radical, TEMPO INTRODUCTION 5-Hydroxymethylfurfural (5-HMF) is a versatile bridge molecule for the production of important platform chemicals from biomass feedstocks [1,2]. 5-HMF can be produced from biomass-derived hexoses and can be further converted into a wide array of valuable furanic chemicals through various catalytic transformations [3-9]. An attractive 5-HMF derivative is 2,5-diformylfuran (2,5-DFF), an important dialdehyde precursor for various pharmaceutical prod- ucts, fungicides, macrocyclic ligands and polymers [10-16]. 2,5-DFF is typically produced from the oxidation of the primary hydroxyl group of 5-HMF. However, improper control in reaction conditions and unsuitable choices of oxidants or catalysts could lead to non- selective oxidation of the hydroxyl and α, β-unsaturated aldehyde groups of 5-HMF. Formation of other 5-HMF oxidation products such as 5-hydroxymethylfuran-2-carboxylic acid (HMFCA), 5-formyl-2- carboxylic acid (FFCA) and 2,5-furandicarboxylic acid (2,5-FDCA) could reduce the reaction selectivity towards 2,5-DFF production [4-6,17]. Furthermore, severe reaction conditions could result in the formation of side products from over-oxidation, decarbonylation and cross-polymerization of 5-HMF [18]. Selective oxidation reactions of 5-HMF to 2,5-DFF are continu- ously being developed with various approaches to minimize side product formation [19]. Recently, vanadium and noble metals like Au, Pt, Ru and complexes like metal/bromide (Co/Mn/Br) have been effectively applied as catalysts for the synthesis of 2,5-DFF and 2,5-FDCA [18,20-26]. Homogeneous oxidants such as Pb(OAC) 4 - pyridine, pyridinium chlorochromate (PCC), K 2 Cr 2 O 7 -DMSO, 2,2,6,6- tetramethylpiperidine-1-oxide (TEMPO) free radicals and NaOCl- Mn (III)-salen complex have also been used for competent synthe- sis of 2,5-DFF [27-32]. But despite the acceptable 2,5-DFF yields, most of the reported systems are metal-based. These reactions often use nocuous solvents as well as require severe reaction conditions (i.e., high temperature and long reaction period); both features do not satisfy the current demands for green and energy-efficient technol- ogies. In this regard, the use of metal-free organic catalysts or oxi- dants appears very interesting. Among various homogeneous catalytic systems, TEMPO free rad- ical derivatives are renowned oxidants with several applications in organic chemistry for the oxidation of primary and secondary alco- hols, sulfides and organometallic compounds [33-36]. TEMPO- mediated oxidation of 5-HMF to furanaldehydes has been reported previously in the presence of hypochlorite as co-oxidants [29]. But hypochlorites result in the formation of toxic chlorinated side prod- ucts [37]. Alternatively, hypervalent iodine compounds, with their affordability and non-toxicity, are popular secondary oxidants [38,39]. Their role in regenerating TEMPO in order to complete the cata- lytic cycle for alcohol oxidation has been demonstrated in several studies [40,41]. This work presents the production of 2,5 DFF from 5-HMF oxida- tion using 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-hy- droxy-TEMPO) radical as a homogeneous oxidant with hypervalent iodine-based secondary oxidant [bis(acetoxy)-iodo]benzene (BAIB) [PhI(OAc) 2 ]. Reactions were intentionally performed in low boiling point solvents (with b.p. ≤100 o C) for convenient and energy-effi- cient recovery of 2,5 DFF. Effects of reaction temperature, time, oxidant dosages and acid addition were examined to achieve accept- able 2,5-DFF yields. MATERIALS AND METHODS 1. Reagents 4-Hydroxy-TEMPO (97 %) and BAIB (98 %) were obtained from Sigma-Aldrich (South Korea). Substrate 5-HMF (98%), product standard 2,5-DFF (>98%) were purchased from Acros Organics