Potassium Persulfate as an Eco-Friendly Oxidant for Oxidative Transformations

Abstract

The formation of carbon-carbon/carbon-heteroatom bonds by oxidative transformations is a hotly debated topic in chemistry. K2S2O8 has emerged as a cost-effective inorganic oxidant for a wide range of oxidative reactions in this setting. This book chapter covers oxidative reactions facilitated by K2S2O8 in the absence of a metal catalyst in detail. Organic chemists may find this book chapter valuable in formulating the mechanistic pathways involving the sulphate radical anion, as well as in the quick and environmentally friendly synthesis of novel chemical species.

1. Introduction

Heterocyclic compounds are fascinating for several reasons, the most notable of which is that they have biological activities, and many drugs are heterocycles. Because of their biological properties, nitrogen heterocycles [1] and oxygen heterocycles (such as coumarins and analogues, [2, 3, 4] as well as chromone-based compounds [5]) have long aroused chemists’ interest. As a result, organic chemists have been hard at work developing new and efficient synthetic transformations to make these heterocyclic compounds. Carbon carbon (C-C)/carbon-heteroatom (C-X) formations are generally used in the synthesis of these heterocycles. The formation of carbon carbon (C-C)/carbon heteroatom (C-X) bonds between two C-H/C-H bonds or C-H/X − H bonds via oxidative transformation has become a central focus in C-C/C-X bond forming reactions in this setting, obviating the use of prefunctionalized substrates and reducing salt waste generation, resulting in superior sustainability and environmental compatibility [6, 7, 8]. Over the last two decades, the reliance on these direct oxidative C-H functionalizations that offer higher atom economy and sustainability has steadily increased, indicating the importance of and growing interest in this synthetic methodology. Despite the inherent difficulty of generating high regio-selectivity, effective realizations of numerous regioselective C − H functionalizations have been accomplished [9, 10]. Transition-metal-catalyzed oxidative reactions are one of the most cutting-edge aspects in organic chemistry. In these reactions, an oxidant is always used to regenerate the catalyst. In several of these metal-catalyzed reactions, it has been discovered that selecting the right terminal oxidant is critical to achieve the desired catalytic result. Molecular oxygen, 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), p-benzoquinone, tert-Butyl hydroperoxide (TBHP), PhI(OAc)₂, Iodine, metal oxidants, oxone, persulfates, and other oxidants have all been found to be useful in these processes. Among these inorganic and organic oxidants, potassium persulfate (K₂S₂O₈) has emerged as a good inorganic oxidant for a wide range of oxidative transformations, with applications spanning from laboratory studies to industrial processes. Since the discovery of the Minisci reaction, K₂S₂O₈ has demonstrated its special utility as an inexpensive, readily available oxidant [11, 12]. Among various peroxygen families of compounds, such as H₂O₂, KHSO₄, and others, the peroxydisulfate ion (S₂O₈²⁻) is the most effective oxidant. In aqueous solution, the standard redox potential is predicted to be 2.01 V [11]. Under mild circumstances, thermal, photolysis, radiolysis, or redox breakdown of S₂O₈²⁻ produces the sulphate radical anion (SO₄^•−) additionally, transition-metal ions can activate K₂S₂O₈ to generate SO₄^•−. With a redox potential of 2.531 V, SO₄^•− is considered an extremely strong one-electron oxidant [13, 14]. Because of their predilection for electron transfer processes, it has a longer lifetime (4 s) than hydroxyl radicals. Exergonic or endergonic electron transport processes exist. Because of the high activation energy, the endergonic process could be sluggish. Various metal salts and complexes, anions, nucleophilic radicals, and neutral organic molecules can all be oxidized by K₂S₂O₈ [11]. In recent years, a plethora of literature has emerged, highlighting the potential use of this oxidant in a variety of metal-catalyzed and metal-free organic reactions. Not only has it found widespread application in palladium catalysis as a result of Minisci’s work, but it has also been used to carry out a variety of novel oxidative transformations without the aid of any metal catalyst. In comparison to K₂S₂O₈, other versions such as Na₂S₂O₈ and (NH₄)₂S₂O₈ are significantly less widely utilized. This is due to the potassium salt’s higher solubility in organic solvents, allowing for more efficient transformation. The C − C to C − X (X = N, O, S, P, B, Si, F, Br, I) bond forming reaction is covered by the spectrum of transformations accomplished with K₂S₂O₈ in metal-catalyzed and metal-free methods across a wide variety of substrates. K₂S₂O₈ has also been shown to be quite effective at degrading organic pollutants, especially aromatic pollutants [15]. Despite the fact that selective organic transformations involving electron transfer to SO₄^•− have been studied in the literature [11, 16, 17], no comprehensive investigation on metal-free oxidative transformations involving persulfate K₂S₂O₈ has been published, including updates on recent progress in the field. The focus of the current book chapter is on the use of K₂S₂O₈ in oxidative organic transformations. Because there is so much information about this oxidant, just the most important examples illustrating a wide range of bond types are provided here. This review is separated into groups based on the types of bonds produced. We hope that chemists working on or planning to work on developing K₂S₂O₈-based approaches for metal-free oxidative processes will find this book chapter useful, permitting considerable scientific advancement in this area.

2. Metal-free oxidative transformations with K₂S₂O₈

K₂S₂O₈ is used as the major oxidant in the creation of a variety of C − C/C − N/C − S/C − O bonds, allowing access to a variety of cyclic and acyclic compounds. In the process of oxidation S₂O₈²⁻ is either directly involved or the radical anion sulphate (SO₄^•−), which, in turn, is produced by the breakdown of K₂S₂O₈.

2.1 C–C bond formation

Direct radical acylation, alkylation, and arylation reactions (through cross-dehydrogenative coupling reactions and decarboxylative processes), cascade radical addition cyclization processes, multifold bond-cleavage-bond-forming reactions, and photoredox reactions are among the various types of C-C bond-forming reactions reported with K₂S₂O₈ as the sole oxidant. K₂S₂O₈-mediated hydroxyalkylation of 2H-benzothiazoles with aliphatic alcohols in aqueous solution was reported by Weng and co-workers [18]. This mild and convenient approach produced a variety of hydroxyalkylated benzothiazoles in moderate to good yields. In addition, benzimidazole and ethers were compatible in this reaction, resulting in C-2 ether-substituted heteroarenes. K₂S₂O₈ not only works as an oxidant in this case, but it also aids in the formation of radicals. In the reaction, there would be cross-coupling between the radicals. In addition, additional radicals would target benzothiazole, so two feasible pathways are proposed in Figure 1. To begin, homolytic cleavage of K₂S₂O₈ produced sulphate radical anions (SO₄^•−), which stripped hydrogens from benzothiazole and alcohol, yielding benzothiazole radical and hydroxyl radical, respectively. The two radicals then had a cross-coupling reaction, resulting in the desired product. The hydroxyl radical, on the other hand, would attack the 2-position of benzothiazole to create radical cation intermediates, which were then deprotonated by SO₄^•− to provide the products (Figure 1) [18].

Figure 1.

K₂S₂O₈-mediated hydroxyalkylation of benzothiazoles with alcohols.

K₂S₂O₈-mediated Minisci acylation on electron-rich pyrroles was used to establish regioselective monoacylation of (NH)-free pyrroles (Figure 2). Under initial heating circumstances, homolytic cleavage of K₂S₂O₈ might form a sulphate radical anion (SO₄^•−), which could then be decarboxylated to produce acyl radical. Two mechanisms could lead to the synthesis of benzoylated product. From the acyl radical, the acylium ion might arise, which could then be electrophilically substituted with pyrrole to create nitrogen radical cation. In other pathway the sulphate radical anion (SO₄^•−) can capture one electron from pyrrole, resulting in pyrrole radical cation, which could produce adduct when reacting with nucleophilic acyl radical. Deprotonation of the intermediate could generate 2-benzoylpyrrole (Figure 3) [19].

Figure 2.

K₂S₂O₈-mediated aroylation of electron-rich pyrroles.

Figure 3.

A mechanism for K₂S₂O₈-mediated aroylation of electron-rich pyrroles.

Wei and colleagues demonstrated a simple, environmentally friendly, and effective method for undertaking radical cyclizations of enynes/dienes in water. This methodology was developed to employ mild reaction conditions with no catalyst, and it was easy to scale up. It was also designed to use K₂S₂O₈ as a green oxidant and water as the solvent, resulting in a process that is both clean and simple to operate, meeting the green chemistry criterion. This reaction undergoes a sequential radical addition, intramolecular cyclization and H-abstraction to give the final product (Figure 4) [20].

Figure 4.

K₂S₂O₈-mediated radical cyclizations of enynes/dienes with alcohols.

Zhang and Chen jointly reported K₂S₂O₈−/tetrabutylammonium hydrogen sulfate (TBAHS) promoted cascade oxidative aryl-alkylation of N-Aryl-alkylation of N-aryl acrylamides for functionalized oxindole synthesis (Figure 5) [21]. Under the heating condition, K₂S₂O₈ interacted with TBAHS to produce bis(tetrabutylammonium) peroxydisulfate, which might undergo homolytic O-O bond cleavage to yield two molecules of tetrabutylammonium sulphate radical anions (n-Bu₄N⁺SO4^•,) [22, 23]. The radical anions then extract a hydrogen atom from a variety of C_sp3-H compounds, resulting in the C-centered radical. Alkene would then grab the resultant radical, which would then be cyclized to form an aryl radical. Finally, a carbocation is formed by single-electron oxidation of resultant aryl radical by radical anions, which is deprotonated by the produced sulphate dianion (n-Bu₄N⁺SO₄²⁻) to obtain the desired product. The active n-Bu4N⁺SO4^•, produced in the first stage of the reaction can provide higher solubility and a suitable oxidation potential for the product.

Figure 5.

K₂S₂O₈ and TBAHS promoted synthesis of oxindoles.

Under metal-, photocatalyst-, and light-free circumstances, the Baishya group described two simple and successful C-3 arylation protocols of quinoxalin-2(1H)-ones with arylhydrazines and aryl boronic acids, respectively, via free radical cross-coupling reactions. Under two separate reaction conditions, K₂S₂O₈ has been employed as an effective oxidant to create aryl radicals from arylhydrazines and aryl boronic acids. The process starts when persulfate S₂O₈²⁻ decomposes into the sulphate radical anion SO₄^•−, which interacts with phenylhydrazine to create the phenylhydrazine radical. Another sulphate anion radical combines with SO₄^•− to produce phenyldiazene, which then reacts with still another sulphate anion radical to produce phenyldiazene radical. The phenyl radical is formed when N₂ gas is removed from phenyldiazene radical, and it conducts a Minisci-type radical addition reaction on the C-3 position of quinoxalin-2(1H)-one, yielding the desired product as shown in Figure 6 [24].

Figure 6.

K₂S₂O₈Mediated C-3 arylation of quinoxalin-2(1H)-ones.

In the presence of persulfate, Ryu’s group found that a wide range of unactivated acyclic and alicyclic substrates cleanly undergo site-selective alkenylation of unactivated C(sp³)-H bonds with 1,2-bis(phenylsulfonyl)ethene. The sulphate radical formed by thermally induced homolysis of the persulfate anion abstracts a hydrogen from the β-position of cyclopentanone to create alkyl radical. After that, this radical combines with the C-C double bond of 1,2-bis(phenylsulfonyl)ethene to generate another radical, which then undergoes β-scission to yield the desired product as shown in Figure 7 [25].

Figure 7.

Persulfate anion-induced C_(sp3)-H alkenylation by 1,2-bis(phenylsulfonyl)ethane.

Inorganic oxidants such as potassium persulfate (K₂S₂O₈) have been frequently employed in oxidative transformations because they are inexpensive and readily available. Tang and Chang’s group published a method for selective intramolecular radical trifluoromethylacylation of alkenes with low-cost CF₃SO₂Na and K₂S₂O₈ to produce CF₃-functionalized chroman-4-ones (Figure 8) [26]. The rate-determining phase entailed the production of trifluoromethyl radical (CF₃) from CF₃SO₂Na via the oxidation of K₂S₂O₈. The reaction was started by CF₃ rather than the acyl radical from the aldehyde, according to control experiments and DFT calculations.

Figure 8.

Synthesis of CF₃-functionalized chroman-4-ones.

Under metal-free circumstances, the Xaio group disclosed a novel and simple approach for the synthesis of 3-(2-oxo-2- arylethyl)chroman-4-ones as shown in Figure 5. Using the radical method, aromatic or aliphatic aldehydes react with various 2-(allyloxy)arylaldehydes to make chroman-4-one derivatives in a moderate to good yields. The procedure is metal-free and has a step-by-step approach, as well as readily available starting materials, demonstrating its some physiologically active chemicals having practical synthetic use (Figure 9) [27].

Figure 9.

K₂S₂O₈- mediated synthesis of chroman-4-one derivatives.

2.2 C–N bond formation

Under metal-free circumstances, several nitration, azidation, and intramolecular C-N bond-forming reactions with K₂S₂O₈ have been described. Unlike the decarboxylation of alkyl radicals from carboxylic acids or the generation of sulfur-centered radicals from the corresponding metal salts, silver or other metal catalysts are not required for the generation of nitrogen dioxide or azide radicals (redox potentials of nitrogen dioxide and azide radicals are +1.04 V and + 1.33 V, respectively), [28, 29] and K₂S₂O₈ alone could suffice.

By employing TBN and various internal alkenes, Patel group developed a metal-free approach with K₂S₂O₈ and quinolone for the synthesis of 1,2,5-oxadiazole-N-oxides (furoxans) and nitrolefins from various internal alkenes as shown in Figure 10 [30]. In this method, the TBN undergoes thermal heterolytic cleavage of tert-butyl nitrite, resulting in the formation of a NO radical and a tert-butoxy radical. Under aerobic reaction conditions, the NO radical is transformed to a NO₂ radical. As shown in Figure 10, the NO₂ radical generated attacks the various alkenes and produces the desired products [30].

Figure 10.

Tert-butyl nitrite mediated differential functionalizations of internal alkenes.

The Sawant group published an excellent yielding transition metal-free technique for oxidative coupling of primary amines to imines and azobenzenes, thiols to disulfides, and 2-aminothiophenols to benzothiazoles. The use of biocompatible and green reaction conditions such as solvent, room temperature reactions, and a transition metal-free approach are among the advantages of the current ecologically friendly process. It also has a wider range of substrate scope (Figure 11) [31].

Figure 11.

K₂S₂O₈-mediated synthesis of imines, azobenzenes, benzothiazoles, disulfides.

2.3 C–O/C–S/C–Se/C–halogen bond formation

The oxidative C-O, C-S, C-Se and C-halogen bond-forming processes utilizing K₂S₂O₈ as the only oxidant are described in some detail. For the synthesis of 1,2-diketones from internal alkynes, Chao and colleagues established a K₂S₂O₈-mediated, transition-metal-free approach [32]. For diaryl- and aryl-alkyl acetylenes, Chao’s procedure is quite convenient. However, under this K₂S₂O₈-mediated reaction state, the aldehyde functionality connected to the aryl-alkyne is unwelcome, resulting in a very poor yield of the desired 1,2-diketone product. Transition-metal (Pd, Ru, Au, Ag, and Cu) catalyzed reactions are generally used to convert alkynes to 1,2-diketones [33, 34]. This K₂S₂O₈-mediated process is a good transition-metal catalyzed reaction alternative. The author concluded from ¹⁸O-isotope labelling tests that oxygen incorporated into alkyne came from K₂S₂O₈ and molecular oxygen rather than water (H₂O¹⁸) as shown in Figure 12 [32].

Figure 12.

K₂S₂O₈-mediated synthesis of 1,2-diketones.

Tetrahydro-carbolines were oxidized by persulfate, according to the Chen group. In moderate to good yields, this reaction promotes the synthesis of a range of 2-formyl N-substituted tryptamines and related derivatives as important intermediates. The approach can be used to perform direct last-stage oxidation of Cialis and evodiamine, two interesting medicines (Figure 13). Under thermolysis in the DMSO solvent, breakdown of S₂O₈²⁻ results in the creation of the sulphate radical anion SO₄^•− single electron transfer (SET) from tetrahydro-carboline to SO₄^•− yields the carbon-centered radical, which is then further oxidized to provide the iminium intermediate. N-Boc-2-formyl-Trp-OH is produced via intermolecular nucleophilic addition to an iminium intermediate (Figure 13) [35].

Figure 13.

K₂S₂O₈-mediated oxidation of tetrahydro-β-carbolines by persulfate.

In order to synthesis the related flavanones and chalcones in good to excellent yields, a novel K₂S₂O₈-mediated approach for the oxidative deoximation of flavanone and chalcone oximes was developed. Flavanone oximes, chalcone oximes, ketoximes, and aldoximes have all been effectively deoximated using this approach. This approach works for both inhibited and functionalized aldoximes as well as ketoximes (Figure 14) [36].

Figure 14.

K₂S₂O₈-mediated oxidative deoximation of oximes.

Bhat recently reported paraselective thiocyanation of phenol and aniline driven by K₂S₂O₈. For heterocycles like indoles, high regioselectivity was also seen (C3-thiocyanation) as shown in Figure 15 [37]. To learn more about the mechanism, the radical scavenger TEMPO (2,2,6,6- tetramethyl-1-piperidinyloxyl) was treated with the reaction mixture. Even after an extended reaction period, the thiocyanation reaction did not progress, indicating that a free radical route was most likely engaged during the process. K₂S₂O₈ is well recognized for producing a powerful, short-lived oxidant-sulphate radical anion (SO₄^•−). When the sulphate radical anion (E^o = 2.6 V) interacts with aromatics with low ionization potential, it produces a radical cation [38, 39].

Figure 15.

K₂S₂O₈-mediated Thiocyanation of phenols, anilines and heterocycles.

Yu reported using thiocyanation and C-O cyclization in the presence of K₂S₂O₈ to obtain 3-thiocyanato-4H-chromen-4-ones from different 2-hydroxyaryl enaminones [40]. The production of a nucleophilic SCN radical was hypothesized as the next step in this process as shown in Figure 16.

Figure 16.

K₂S₂O₈-mediated synthesis of 3-thiocyanato-4H-chromen-4-ones.

Sun and co-workers described a K₂S₂O₈-mediated selenoamination of alkenes using diphenyl diselenide and several nitrogen containing compounds such as saccharin, dibenzenesulfonimide, benzotriazole, pyrazole, 1,2,4-triazole, 6-chloropurine, and others as shown in Figure 17 [41].

Figure 17.

K₂S₂O₈-promoted selenoamination of alkenes.

Yi and co-workers used Selectfluor and K₂S₂O₈ to develop a transition-metal-free technique for direct benzylic C-H fluorination [31]. Despite the existence of different techniques for this transformation, the use of K₂S₂O₈ as a cheap oxidant was shown to be the most effective. The most plausible scenario was the formation of a benzylic radical with the sulphate radical ion, which then interacted with a F atom from Selectfluor (Figure 18) [39].

Figure 18.

K₂S₂O₈-promoted benzylic monofluorination and difluorination.

3. Conclusions

Oxidative transformations that result in the formation of C-C/C-X bonds are an important class of reactions that has made significant progress in recent years. The oxidative reactions carried out under metal-free conditions using K₂S₂O₈ as the major oxidant are highlighted in this book chapter. Overall, this book chapter covers a wide range of greener metal-free transformations (C-C, C-N, C − O/C − S/C − Se/C − Halogen bond formations) with K₂S₂O₈ and the mechanisms that underpin them. Their applications in visible light and photoredox-catalyzed reactions have recently been discovered. Nonetheless, given the current state of knowledge about the use of this oxidant in diverse transformations, a comeback of new techniques is very likely in the near future, which can be hastened even further with a complete grasp of mechanistic pathways.

Acknowledgments

Bilal Ahmad Mir acknowledges the support of this chapter by University Grants Commission (CH/20-21/0228) for Fellowship. Suresh R acknowledges the support of this chapter by SERB for funding under the National Post-Doctoral Fellowship scheme SERB-NPDF (PDF/2021/002055) and Rajamalli P, MRC, IISc Bangalore for providing RA position.

Conflict of interest

The authors declare no conflict of interest.