Azidodifluoromethanide (N3CF2-): In Situ Generation and Nucleophilic Addition to Aldehydes.

A facile one-pot approach for the azidodifluoromethylation of aldehydes via in situ-generated azidodifluoromethenide (N3CF2-) utilizing commercially available TMSCF2Br and NaN3 is disclosed. The formed O-silyl ether products are obtained in yields of up to 91% in short reaction times at ambient temperature. Examples of both inter- and intramolecular [3 + 2] azide-alkyne cycloaddition reactions of the installed azidodifluoromethyl handles are also presented, demonstrating the prospective synthetic and biochemical functionality and utility.

Addition of Imidazolium-Based Ionic Liquid to Improve Methanol Production in Polyamine-Assisted CO2 Capture and Conversion Systems Using Pincer Catalysts.

Ionic liquids have been studied as CO2 capture agents. However, they are rarely used in combined CO2 capture and conversion processes. Utilizing imidazolium-based ionic liquids, the conversion of CO2 to methanol was greatly improved in polyamine assisted systems catalyzed by homogeneous pincer catalysts with Ru and Mn metal centers. Among the ionic liquids tested, [BMIM]OAc was found to perform the best under the given reaction conditions. Among the polyamine tested, pentaethylenehexamine (PEHA) led to the highest conversion rates. Ru-Macho and Ru-Macho-BH were the most active catalysts. Direct air capture utilizing PEHA as the capture material was also demonstrated and produced an 86 % conversion of the captured CO2 to methanol in the presence of [BMIM]OAc.

Integrated Carbon Dioxide Capture and Conversion to Methanol Utilizing Tertiary Amines over a Heterogenous Cu/ZnO/Al2O3 Catalyst.

Increasing carbon dioxide emissions has sparked a growing interest in capturing these emissions at the source of their release. For such processes, amines can be used as carbon dioxide capture agents. Herein, CO2 was captured under ambient conditions using solutions of amines and polyamines in ethylene glycol. The captured solutions were then successfully hydrogenated to methanol under hydrogen pressure with a heterogeneous Cu/ZnO/Al2O3 industrial catalyst. An extensive amine scope found that tetramethyl-1,6-hexanediamine, with two tertiary amine sites, provided the highest methanol productivity. This reaction was then optimized to achieve up to 89% methanol yield under relatively mild conditions of 250 °C and 80 bar H2 pressure. The catalyst was shown to be recyclable over five reaction cycles.

Recent Advances in Visible Light-Mediated Radical Fluoro-alkylation, -alkoxylation, -alkylthiolation, -alkylselenolation, and -alkylamination.

In the last few years, many reagents and protocols have been developed to allow for the efficient fluorofunctionalization of a diverse set of scaffolds ranging from alkanes, alkenes, alkynes, and (hetero)arenes. The concomitant rise of organofluorine chemistry and visible light-mediated synthesis have synergistically expanded the fields and have mutually benefitted from developments in both fields. In this context, visible light driven formations of radicals containing fluorine have been a major focus for the discovery of new bioactive compounds. This review details the recent advances and progress made in visible light-mediated fluoroalkylation and heteroatom centered radical generation.

Photoredox Catalysis for the Synthesis of N-CF2 H Compounds Using 1-((N-(difluoromethyl)-4-methylphenyl)-sulfonamido)pyridin-1-ium Trifluoromethanesulfonate.

N-(difluoromethyl)amino (-NCF2 H) compounds are of great interest given their unique and underexplored physiochemical properties. The lack of structural diversity in NCF2 H compounds is likely due in part to the shortage of protocols for efficient installation. Presented herein is a new shelf-stable pyridinium reagent that enables the direct installation of the N-(difluoromethyl)sulfonamide moiety [N(Ts)CF2 H)] onto (hetero)arenes and alkenes for the diversification of aryl and alkyl NCF2 H compounds. The described protocol utilizes blue light photoredox catalysis and displays broad functional group tolerance with excellent chemoselectivity. Additional transformations and applicability towards a photoredox continuous flow protocol are also demonstrated.

Copper-Catalyzed Synthesis of Difluoromethyl Alkynes from Terminal and Silyl Acetylenes.

An efficient method for the direct C(sp)-H difluoromethylation of terminal alkynes and the desilylation-difluoromethylation of (trimethylsilyl)acetylenes is disclosed. The copper-catalyzed transformation provides access to a wide range of structurally diverse CF2H alkynes in good yields, utilizing a (difluoromethyl)zinc reagent and an organic oxidant. The difluoromethylation of important synthons and API's is showcased. The synthetic utility of these (difluoromethyl)alkynes is demonstrated by selected cycloaddition reactions. Additionally, a slight modification to the reaction conditions allowed the selective preparation of a 2-difluoromethylindole.

Homogeneous Hydrogenation of CO2 and CO to Methanol: The Renaissance of Low-Temperature Catalysis in the Context of the Methanol Economy.

The traditional economy based on carbon-intensive fuels and materials has led to an exponential rise in anthropogenic CO2 emissions. Outpacing the natural carbon cycle, atmospheric CO2 levels increased by 50 % since the pre-industrial age and can be directly linked to global warming. Being at the core of the proposed methanol economy pioneered by the late George A. Olah, the chemical recycling of CO2 to produce methanol, a green fuel and feedstock, is a prime channel to achieve carbon neutrality. In this direction, homogeneous catalytic systems have lately been a major focus for methanol synthesis from CO2 , CO and their derivatives as potential low-temperature alternatives to the commercial processes. This Review provides an account of this rapidly growing field over the past decade, since its resurgence in 2011. Based on the critical assessment of the progress thus far, the present key challenges in this field have been highlighted and potential directions have been suggested for practically viable applications.

Visible-Light Photoredox-Catalyzed C(sp2)-H Difluoromethoxylation of (Hetero)arenes Utilizing a Shelf-Stable Pyridinium Reagent.

Difluoromethoxyarene moieties have been demonstrated to impart desirable physio-chemical properties to organic molecules. Presented herein is a shelf-stable radical difluoromethoxylating reagent that enables facile and direct C(sp2)-H difluoromethoxylation of (hetero)arenes under blue light photoredox catalysis. 4-Cyano-1-(difluoromethoxy)pyridin-1-ium trifluoromethanesulfonate is prepared in one simple step from the parent pyridine N-oxide. The current protocol tolerates a variety of synthetically and pharmacologically relevant functional groups. Applicability toward the late-stage functionalization of APIs and druglike molecules is also demonstrated.

gem-Halofluorocyclopropanes via [2 + 1] Cycloadditions of In Situ Generated CFX Carbene with Alkenes.

An efficient and operationally simple synthesis of gem-bromofluorocyclopropanes under mild conditions has been developed. The method employs ethyl dibromofluoroacetate (EDBFA) as an accessible and inexpensive source of the bromofluorocarbene (:CFBr) intermediate. The protocol provides the bromofluorocyclopropane products in excellent yields, including examples synthesized in multigram scales. The chlorinated ester, ethyl dichlorofluoroacetate (EDCFA), is also utilized to make the analogous gem-chlorofluorocyclopropanes.

Nickel and Copper Catalyzed ipso-Phosphonodifluoromethylation of Arylboronic Acids with BrCF2 P(O)(OEt)2 for the Synthesis of Phosphonodifluoromethylarenes.

A convenient method for the direct ipso-phosphonodifluoromethylation of arylboronic acids via nickel-copper co-catalysis is disclosed. This work, which utilizes inexpensive first row transition metals, represents a facile alternative to the traditional palladium catalyzed approach. The method utilizes inexpensive commodity chemicals and substrates while tolerating a variety of biologically relevant functional groups. Structurally diverse phosphonodifluoromethylarenes are furnished in good yields under short reaction times. Control experiments to probe possible reaction pathways are also included.

Collapsing Glomerulopathy Superimposed on Diabetic Nephropathy.

Diabetic nephropathy (DN) is characterized by progressive increase in proteinuria and decline in renal functions. Various forms of nondiabetic kidney disease may be superimposed on DN, which can alter the progression of DN. Collapsing glomerulopathy (CG) may superimpose on DN, and is characterized by rapid worsening of renal failure and has poor prognosis. In our institute, renal biopsies were performed in diabetic patients for increasing proteinuria or worsening renal functions. There were seven cases of CG superimposed on DN. All patients except one had a history of long standing diabetes mellitus. All patients had nephrotic range proteinuria. Four patients had severe renal failure at presentation. Renal biopsy showed CG superimposed on DN. Six patients progressed to end-stage renal disease during follow-up; one patient is in chronic kidney disease-stage 3b. The development of CG contributes to an increased level or new onset proteinuria in DN, and can lead to rapid worsening of renal failure. The diagnosis of CG superimposed on DN is of prognostic significance.

Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions.

A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed.

Chemoselective N- and O-Difluoromethylation of 2-Pyridones, Isoquinolinones, and Quinolinones with TMSCF2Br.

An operationally simple protocol for direct N- and O-difluoromethylation of 2-pyridones, quinolinones, and isoquinolinones using commercially available TMSCF2Br is disclosed. The chemoselectivity is modulated by simple variations in temperature, solvent, and strength of the base. Diverse, synthetically relevant functional groups are tolerated, including functional groups that have reported reactivity with TMSCF2Br. Gram-scale reactions to prepare both N- and O-difluoromethyl compounds are included.

A Case of Hearing Impairment with Renal Dysfunction.

Hearing impairment in a patient with renal failure is an important clue towards etiologic diagnosis of kidney disease. Variety of hereditary diseases, developmental defects, and toxins involve these two organs. However, additional retinopathy is seen in quite a few diseases which include Alport's syndrome and Muckle-Wells syndrome (MWS). We are reporting a case of middle-aged woman with childhood-onset of hearing impairment who presented with renal failure and was diagnosed to have renal amyloidosis on kidney biopsy but without any light chain restriction. During evaluation for live donor kidney transplant, her brother was also found to have hearing impairment and retinopathy however with normal renal function and urinalysis. Genetic testing of both of them was done for panel of mutations related to hereditary amyloidosis which revealed NLRP3 mutation in both. This mutation is characteristic of MWS which can lead to secondary amyloidosis and renal failure.

Tertiary Amine-Ethylene Glycol Based Tandem CO2 Capture and Hydrogenation to Methanol: Direct Utilization of Post-Combustion CO2.

Carbon dioxide capture using tertiary amines in ethylene glycol solvent was performed under ambient conditions. Subsequently, the CO2 captured as alkyl carbonate salts was successfully hydrogenated to methanol, in the presence of H2 gas and Ru-Macho-BH catalyst. A comprehensive series of tertiary amines were selected for the integrated capture and conversion process. While most of these amines were effective for CO2 capture, tetramethylethylenediamine (TMEDA) and tetramethylbutanediamine (TMBDA) provided the best CH3 OH yields. Deactivation of the base due to side reactions was significantly minimized and substantial base regeneration was observed. The proposed system was also highly efficient for CO2 capture from a gas mixture containing 10 % CO2 , as found in flue gases, followed by tandem conversion to CH3 OH. We postulate that such high boiling tertiary amine-glycol systems as dual capture and hydrogenation solvents are promising for the realization of a sustainable and carbon-neutral methanol economy in a scalable process.

Hevea brasiliensis mediated synthesis of nanocellulose: Effect of preparation methods on morphology and properties.

In present research, Hevea brasiliensis (Rubber Wood) converted into cellulose by pre-treatment with NaOH (5%) and NaClO2 (5%). In addition, the cellulose was converted to nanocellulose (NC) using ionic liquid, acid hydrolysis and TEMPO oxidation accompanied by ultra-sonication. The prepared nanocellulose characterized by X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Fourier transformation infrared spectroscopy (FT-IR). Thermal properties have been studied using thermogravimetric and differential thermal Analysis (TGA/DTA). FT-IR results clearly suggested that the synthetic approaches employed did not alter the principle chemical structure of rubber wood cellulose. SEM and AFM monographs reveal that synthetic approaches affect the morphology/surface topology of prepared nanocellulose. Among the three kinds of NC, NC by TEMPO approach had the largest aspect ratio and superior thermal stability.

Protonation of CH3 N3 and CF3 N3 in Superacids: Isolation and Structural Characterization of Long-Lived Methyl- and Trifluoromethylamino Diazonium Ions.

The methylamino diazonium cations [CH3 N(H)N2 ]+ and [CF3 N(H)N2 ]+ were prepared as their low-temperature stable [AsF6 ]- salts by protonation of azidomethane and azidotrifluoromethane in superacidic systems. They were characterized by NMR and Raman spectroscopy. Unequivocal proof of the protonation site was obtained by the crystal structures of both salts, confirming the formation of alkylamino diazonium ions. The Lewis adducts CH3 N3 ⋅AsF5 and CF3 N3 ⋅AsF5 were also prepared and characterized by low-temperature NMR and Raman spectroscopy, and also by X-ray structure determination for CH3 N3 ⋅AsF5 . Electronic structure calculations were performed to provide additional insights. Attempted electrophilic amination of aromatics such as benzene and toluene with methyl- and trifluoromethylamino diazonium ions were unsuccessful.

Hydroxide Based Integrated CO2 Capture from Air and Conversion to Methanol.

The first example of an alkali hydroxide-based system for CO2 capture and conversion to methanol has been established. Bicarbonate and formate salts were hydrogenated to methanol with high yields in a solution of ethylene glycol. In an integrated one-pot system, CO2 was efficiently captured by an ethylene glycol solution of the base and subsequently hydrogenated to CH3OH at relatively mild temperatures (100-140 °C) using Ru-PNP catalysts. The produced methanol can be easily separated by distillation. Hydroxide base regeneration at low temperatures was observed for the first time. Finally, CO2 capture from ambient air and hydrogenation to CH3OH was demonstrated. We postulate that the high capture efficiency and stability of hydroxide bases make them superior to existing amine-based routes for direct air capture and conversion to methanol in a scalable process.

Aqueous Base Promoted O-Difluoromethylation of Carboxylic Acids with TMSCF2Br: Bench-Top Access to Difluoromethyl Esters.

A method for the O-difluoromethylation of carboxylic acids using commercially available TMSCF2Br is disclosed. The devised benchtop reaction system is air-stable and offers mild reaction conditions while using readily available reagents and solvents. The method is applicable to both aliphatic and aromatic carboxylic acids while demonstrating compatibility with a range of commonly encountered functional groups. The difluoromethyl esters of FDA approved drugs and pharmaceutically relevant molecules are also presented, demonstrating the potential for late-stage functionalization.