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An efficient iodine-imine synergistic promoted Povarov-type multicomponent reaction was reported for the synthesis of a practical 2,2'-biquinoline scaffold. The tandem annulation has reconciled iodination, Kornblum oxidation, and Povarov aromatization, where the methyl group of the methyl azaarenes represents uniquely reactive input in the Povarov reaction. This method has broad substrate scope and mild conditions. Furthermore, these 2,2'-biquinoline derivatives had been directly used as bidentate ligands in metal-catalyzed reactions.

A new strategy has been developed for the synthesis of 2,5-disubstituted oxazoles from easily available arylacetylenes and α-amino acids in the presence of Cu(NO3)2•3H2O and iodine. This reaction ­process involves the I2/Cu(NO3)2•3H2O-assisted transformation of ­arylacetylene to α-iodo acetophenone, Kornblum oxidation to phenylglyoxal, condensation to imine, decarboxylation/annulation/oxidation reaction sequence to approach 2,5-disubstituted oxazoles.

This review article focuses on the α-functionalization of acetophenones involving Kornblum oxidation and C–H functionalizations. Although various other strategies, such as classical approaches, enamine approaches and umpolung strategy are also known for this functionalization, here we discuss mainly the Kornblum oxidation approach and C–H functionalization strategy as they have advantages over the others. In Kornblum oxidation, the reaction uses iodine and dimethylsulfoxide and proceeds through the formation of arylglyoxal as the key intermediate. In C–H functionalization, the reaction requires metal, or metal-free catalyst, and generates radical intermediate in most cases. α-Functionalization of acetophenones is very important because of their huge applications in the synthesis of various natural products and pharmaceuticals and, therefore, a number of research articles have been published in this area. However, no review articles are available so far. In this article, we present a succinct discussion of various important and novel reactions, along with their mechanisms, published since 2012 to date. We believe that this first review article in this field will give readers one-stop information on this topic and encourage further intriguing work in this area.

Kornblum oxidation (benzyl bromide to benzaldehyde) can be realized efficiently by NaOH-modified graphitic carbon nitride (g-C3N4). Different from the oxidation reaction carried out at high temperature using DMSO as an oxidant, our reaction is eco-friendly because it is carried out at room temperature under LED light irradiation using molecular oxygen as an oxidant, which avoids the problems of toxicity, pollution and purification. Alkali treatment leads to the surface deprotonation of g-C3N4 to form NaOH-modified g-C3N4 (Na/g-C3N4). The modifications of the electronic structure and surface chemical environment of g-C3N4 facilitate light absorption and formation of ˙O2− and therefore make the conversion of benzyl bromide reach up to 99%. This work demonstrates a green and sustainable route for benzaldehyde production and the superiority of g-C3N4 for organic syntheses.

Owing to excellent selectivity, high yield and stability towards over-reduction and over-oxidation, one of the impressive approaches to synthesize aldehydes and ketones is the oxidation of halomethyl groups. Numerous halomethyl oxidation-based methodologies to afford aldehydes and ketones are disclosed in the literature. Mostly, chloromethyl or bromomethyl group containing substrates have been used in the literature for performing oxidation. There are negligible data available in the literature that addresses the use of iodomethyl group containing substrates for transformation to aldehydes and ketones. In this research work, 110 reactions have been carried out to construct aldehydes and ketones from oxidation of iodomethyl group in benzylic iodides and allylic iodides using numerous well-known approaches reported in the literature. The classical approaches under observation include Sommelet oxidation, Krohnke oxidation, sodium periodate-mediated oxidative protocol, manganese dioxide-based oxidative approach, Kornblum oxidation and Hass–Bender oxidation. The eco-friendly approaches under observation include periodic acid-based IL protocol, periodic acid in vanadium pentoxide-mediated IL method, hydrogen peroxide in vanadium pentoxide-based approach and bismuth nitrate-promoted IL technique. In this investigation, yield, recyclability, cost-effectiveness, eco-friendliness and over-oxidation are the main parameters which are under observation. Among all these investigated techniques, periodic acid-based IL protocol, periodic acid in vanadium pentoxide-mediated IL method and hydrogen peroxide in vanadium pentoxide-based approach (aka. Chunbao oxidation protocol) were found to be highly efficient due to the following reasons: these approaches (1) provide excellent yields, (2) do not lead towards over-oxidation, (3) show good recyclability, (4) demonstrate high thermal stability and negligible flammability, and (5) require no special handling.

The simple and facile strategy for the synthesis of 2,3-disubstituted-chromeno[4,3-b]pyrrole-4(1H)-ones has been established. This method describes the Kornblum oxidation reaction of acetophenones, followed by the Knoevenagle treatment of the resulted (het)arylglyoxals with active methylene compounds and consequently iodine-activated Michael type reaction with 4-amino coumarin in a one-pot manner to afford disubstituted chromeno[4,3-b]pyrrole-4(1H)-one derivatives.

Iodine-promoted oxidative C-H/C-H cross-coupling of unprotected anilines and 2-methylquinoline to furnish C4-carbonylated aniline (4-aminophenyl)(quinoline-2-yl) methanones in moderate to good yields has been demonstrated. This work provides the first site-selective approach for the synthesis of free amino groups containing methanones including unprecedented C-H functionalization rather than the N-H functionalization of unprotected anilines via the Kornblum oxidation of 2-methylquinoline. Furthermore, we noticed that the incorporation of KOH under standard conditions provides 2-heteroarylbenzothiazoles from benzothiazoles and 2-methylquinoline in good to excellent yields. These transformations do not require any transition metals or peroxides and tolerate various functional groups such as methoxy, hydroxy, bromo, chloro and nitro groups. Moreover, a plausible mechanistic pathway is proposed.

Iodine/TBHP/DMSO mediated oxidative rearrangement of 3-styrylquinoxalin-2(1H)-one led to the formation of 3-aroylquinoxalin-2(1H)-ones in good to high yields via Kornblum oxidation. This methodology proceeds under mild conditions via oxidative aryl migration, followed by C C bond cleavage and does not make use of any metal.

An efficient one-pot synthetic procedure has been developed for the preparation of heteroarenyl-benzimidazoles via oxidative Csp3-H functionalization with o-phenylenediamine using I2-DMSO in open air from easily available starting materials. Based on a logical plan a spectrum of multi fundamental reactions like iodination, Kornblum oxidation and amination were brought into one-pot. By using this simple method a library of heteroarenyl-benzimidazoles derivatives (3a-t and 5a-g) and heteroarenyl-benzothiazole (3u) have been synthesized in good to excellent yield and screened for their cytotoxicity against a group of four human cancer cell lines. Among them 3h, 3q and 5b showed significant cytotoxic activities with an IC50 of 1.69, 1.62 and 2.81µM respectively against lung cancer (A549) cell line.

A synergistic I2/amine promoted formal [4 + 2] cycloaddition of methyl ketones, arylamines, and aryl(alkyl)acetaldehydes as alkene surrogates has been established. This protocol allowed the modular synthesis of various 2-acyl-3-aryl(alkyl)quinolines, rather than 2,4-substituted quinolines. Notably, the arylamines not only participated as reactants in this reaction but also acted as indispensable catalysts to promote enamine formation. Moreover, mechanistic investigation suggested that the reaction occurred via an iodination/Kornblum oxidation/Povarov/aromatization sequence.

Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin (2) and results of quantum chemical calculations have shown that this derivative exists in the keto rather than in the enol tautomer 2a. The in vitro antimicrobial activity of 2 was approximately two times weaker in comparison with oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp. strains and similar activity against certain filamentous fungi. The docking binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding affinity for 2 when compared with oligomycin A; that correlated with its activity against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in vitro antiproliferative activities of 2 are also discussed.

A highly efficient I2-promoted formal [4 + 2] cycloaddition has been developed for the synthesis of 2-acylquinolines from methyl ketones and arylamines using 1,4-dithane-2,5-diol as an ethylene surrogate. Moreover, the investigation of the mechanism suggested that this reaction occurred via an iodination/Kornblum oxidation/Povarov/aromatization sequence. It is noteworthy that the arylamine substrate also played an important role in promoting the reaction.

Background: 1,2,4-Triazine is a prominent structural core system present in numerous natural and synthetic biologically active compounds. The existing synthetic methodologies have mostly focused on 3,6-disubstituted-1,2,4-triazines and 3,5,6-trisubstituted-1,2,4-triazines. However, until now only a few methods have been developed for making 3,5-disubstituted-1,2,4-triazines. Objective: The primary objective of the study was to find an efficient and simple way to construct 3,5-disubstituted-1,2,4-triazines. Method: The arylethene (0.24 mmol), I-2 (0.22 mmol), IBX(0.24mmol.) and DMSO (2 mL) were added to a round-bottomed flask equipped with a magnetic stirring bar. The reaction mixture was agitated at 110 degrees C under air for 3h, then amidrazone (0.2 mmol) was added to the mixture and the reaction continued at 110 degrees C for another 1.5h. Afterwards, water (20mL) was added and the reaction mixture was extracted with ethyl acetate (3 x 50mL). The organic phases was combined and concentrated under reduced pressure to distill ethyl acetate. The residue was further purified by column chromatography on a silica gel column with petroleum/ethyl acetate (5:1) as eluent to obtain the desired products. Results: We developed an operationally simple way of regioselectively synthesizing 3,5-disubstituted-1,2,4-triazines by a coupled domino strategy with terminal aryl alkenes and amidrazones in one-pot. The overall process involves three different reactions: iodination, Kornblum oxidation and condensation. Conclusion: The strategies exhibit high performance with moderate to high yields, using simple and readily available terminal aryl alkenes and amidrazones, representing a powerful tool for the formation of potentially biologically active derivatives.

A new fluorescent sensor ( FC4 ) based on fluorescein dithia-cyclic skeleton was designed and prepared as a fluoroionophore for the optical and visual-eye detections of Hg 2+ in aqueous buffer solution. FC4 was prepared via Kornblum oxidation, ester hydrolysis, alkylation, imine formation and imine reduction. The sensor provided highly sensitive and selective ON–OFF fluorescence sensing toward Hg 2+ and was shown to discriminate various interfering metal ions, particularly Cu 2+ and Pb 2+ as well as Al 3+ , Ba 2+ , Ca 2+ , Cd 2+ , Fe 3+ , K + , Mg 2+ , Mn 2+ , Na + and Ni 2+ . Sensor FC4 also exhibited chromogenic change upon binding to Hg 2+ , which served as a “visual-eye” indicator which could be observed as a noticeable change of the solution color from yellow to orange. The Hg 2+ detection limit of the sensor was 7.38 × 10 −9 or 1.48 ppb which was lower than a permissible concentration of Hg 2+ in drinking water regulated by the United States Environmental Protection Agency (U.S. EPA).

A photoredox-catalyzed iminyl radical-triggered C–C bond cleavage/addition/Kornblum oxidation cascade of cycloketone oxime esters and styrenes in DMSO is described. This three-component, one-pot procedure features mild conditions, a broad substrate scope, and high functional group tolerance, providing an efficient approach to access diversely functionalized ketonitriles.

An iodine-promoted sequential dual oxidative Csp3–H amination of aryl methyl ketones and Csp3–H iodination of pyridin-2-ylmethylamines have been realized for the first time. This simple and efficient approach constructed 1-iodoimidazo[1,5-a]pyridines in moderate to good yields. Based on the preliminary experimental results, a self-sequenced process featuring the iodination/Kornblum oxidation/dual amination/oxidation/iodination mechanism was proposed.

A molecular iodine mediated oxidative cross-coupling of β-keto ester sp3 C–H with 1H-indole sp2 C–H was developed for the synthesis of indolo[2,3-b]carbazoles. A self-sequenced iodination/Kornblum oxidation/hydrolyzation/decarboxylative/deacylation/aromatization mechanism has been proposed as a possible reaction sequence to account for the results observed in this study.

A simple, highly efficient and selective oxidative cross coupling of imidazo[1,2-a]pyridine (IP) compounds (1) and methylketones (2), promoted by molecular iodine in DMSO in the presence of a catalytic amount of PTSA has been realized in a one pot reaction. This strategy has provided a general route for the synthesis of 1-aryl-2-(2-phenylimidazo[1,2-a]pyridin-3-yl)ethane-1,2-diones (3) with a new C–C bond formation through Kornblum oxidation followed by nucleophilic attack of IP compounds (1) on the in situ formed phenylglyoxal. Simple reaction conditions, no metal catalysts and selective product formation are the advantages of this protocol.

Methylthio-substituted maleimides are synthesized by a novel annulation strategy from methyl ketones, actetamides, and DMSO in the presence of I2 via an iodination/Kornblum oxidation/amidation/cyclization sequence.

Synthesis of isatin and iodoisatin from 2′-aminoacetophenone was achieved via oxidative amido cyclization of the sp3 C–H bond using I2–TBHP as the catalytic system. The reaction proceeds through sequential iodination, Kornblum oxidation, and amidation in one pot. This method is simple, atom economic, and works under metal- and base-free conditions.

A highly efficient and selective molecular iodine-promoted oxidative cross-coupling/annulation between 2-naphthols and methyl ketones has been realized. The reaction successfully constructed a new quaternary carbon center within 3(2H)-furanones. Our synthetic strategy provided an in situ iodination-based oxidative coupling pathway. Based on the experimental results, a self-sequenced iodination/Kornblum oxidation/Friedel-Crafts/oxidation/cyclization mechanism was proposed.

Janus particles possess heterogeneous surface chemistries which can potentially enhance their interfacial activity and be exploited as useful catalysis agent. It is challenging to control the geometry of the Janus particles and to produce Janus particles in large quantities. In this report, we use a general approach of emulsion swelling assisted protrusion to synthesize the Janus composite particles of titania – poly (vinylbenzyl chloride-divinylbenzene) (TiO 2 -poly (VBC–DVB)). The size of the lobe of poly (VBC–DVB) is tunable. After a series of reactions, including Kornblum oxidation reaction and Tollens’ reaction, the target product of TiO 2 –Ag Janus composite particles is obtained.

A molecular iodine mediated oxidative cross-coupling of β-keto ester sp3 C–H with 1H-indole sp2 C–H was developed for the synthesis of indolo[2,3-b]carbazoles. A self-sequenced iodination/Kornblum oxidation/hydrolyzation/decarboxylative/deacylation/aromatization mechanism has been proposed as a possible reaction sequence to account for the results observed in this study.

An efficient one-pot synthetic protocol has been proposed for the synthesis of luntonin F from easily available starting materials. Through a rational logical design, multifundamental reactions (iodination, Kornblum oxidation, and annulation) were assembled in one-pot. The developed approach can efficiently synthesize luntonin F and a diversity of analogues.

A novel protocol for the synthesis of quinoxalines has been developed from simple ketones and 1,2-diamines. This process underwent a logic approach to bis-substituted quinoxalines via a consecutive iodination/Kornblum oxidation/cyclization in the presence of I2/CuO/DMSO and to mono-substituted quinoxalines via an iodination/cyclization/aromatization in the presence of I2/CuO/K3PO4·3H2O.