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Reductive amination of aldehydes and ketones with nitro compounds. (a) Overall reaction scheme. (b) Mechanism. (c) Methods. (d) Bioactive products synthesized by reductive alkylation of nitro compounds.
Source publication
Reductive amination of carbonyl compounds with primary amines is a well-established synthetic methodology for the selective production of unsymmetrically substituted secondary and tertiary amines. From the industrial and green chemistry perspective, it is attractive to combine reductive amination with the synthesis of primary amines in a single one...
Citations
... 53 Before C─N coupling, nitro compounds were usually exploited as precursors to form nucleophilic amines. 54 As mentioned previously, the reductive amination process for synthesizing primary amines was often accompanied by the formation of secondary amines and tertiary amine byproducts, which posed a straitened circumstance for subsequent C─N coupling reactions. Therefore, enhancing the selectivity of reducing agents (catalysts) remains a significant challenge. ...
Thermochemical conversion of fossil resources into fuels, chemicals, and materials has rapidly increased atmospheric CO 2 levels, hindering global efforts toward achieving carbon neutrality. With the increasing push for sustainability, utilizing electrochemical technology to transform CO 2 or biomass into value‐added chemicals and to close the carbon cycle with sustainable energy sources represents a promising strategy. Expanding the scope of electrosynthesis technology is a prerequisite for the electrification of chemical manufacturing. To this end, constructing the C─N bond is considered a priority. However, a systematic review of electrocatalytic processes toward building C─N bonds using CO 2 and biomass as carbon sources is not available. Accordingly, this review highlights the research progress in the electrosynthesis of organic nitrogen compounds from CO 2 and biomass by C─N coupling reactions in view of catalytic materials, focusing on the enlightenment of traditional catalysis on C─N coupling and the understanding of the basis of electrochemical C─N coupling. The possibility of C─N bond in electrocatalysis is also examined from the standpoints of activation of substrates, coupling site, mechanism, and inhibition of hydrogen evolution reaction (HER). Finally, the challenges and prospects of electrocatalytic C─N coupling reactions with improved efficiency and selectivity for future development are discussed.
... The oxidation of benzyl alcohols plays a crucial role in organic transformations and finds extensive applications across various industries [17,18]. This transformation represents a fundamental step in the synthesis of a wide array of organic compounds [19][20][21][22]. However, traditional oxidation methods typically involve the use of environmentally harmful substances, often leading to the unwanted formation of toxic metal waste. ...
In recent research, there has been a surging interest in green methods for manufacturing metal oxide photo-catalysts and enabling organic transformations in gentle conditions. This study achieved a groundbreaking development, introducing zinc oxide nanoparticles sensitized with anthocyanin dye (ATH-ZnONPs) for the very first time. The reducing agents in pomegranate leaves were utilized to synthesize ZnONPs from zinc salt. Simultaneously, anthocyanin dye was extracted from pomegranate flowers and linked with the ZnONPs. The FT-IR functional group analysis provided evidence of the successful conjugation of ZnONPs and ATH dye. SEM, EDX, and Elemental Mapping analysis unveiled the spherical morphology and nanocrystalline structure of ATH-ZnONPs, with particle sizes falling within the range of 50-70 nm. XRD analysis verified the hexagonal structural configuration of ZnONPs within the hybrid nanocomposite, with calculated lattice parameters of a = 3.261 Å and c = 5.207 Å. UV-Vis and DRS spectroscopy demonstrated that the composite efficiently harnesses visible light irradiation, exhibiting an energy bandgap of 2.22 eV. The assessment of ZnONPs through BET analysis unveiled a pore volume of 0.053 cm3/g, an SSA of 14.223 m2/g, and an average pore size of 4.18 nm, underscoring the mesoporous characteristics of ZnONPs. Importantly, the photocatalytic performance of the synthesized ATH-ZnONPs was thoroughly examined under blue LED light exposure. This investigation encompassed the evaluation of catalyst dosage, the impact of the light source, stability, regeneration, and the potential for reuse in the aerobic oxidation of benzyl alcohols, resulting in their corresponding aldehydes and ketones. 1H NMR and 13C NMR were used to characterize the products. The results of these studies highlight the versatile potential of this composite for a wide range of photocatalytic applications.
... Reductive amination is an important and versatile organic reaction that finds extensive applications in sustainable synthetic processes and has been intensively investigated in both academia and industry [1,2]. Mechanistically, the reaction begins with a condensation step in which the carbonyl compound reacts with ammonia or an amine to form the corresponding imine, followed by reduction of the imine to the alkylamine product [3]. ...
Reductive amination is a powerful tool in sustainable organic synthesis that allows chemists to access a wide range of valuable amine products using renewable feedstocks and mild reaction conditions, with minimal waste generation. Practical applications can be found in various fields, including pharmaceuticals, contributing to greener and more sustainable chemical processes. In this work, we present a heterogeneous (Rh and Pt) catalyzed protocol for the fast and efficient synthesis of ractopamine hydrochloride (β-adrenergic drug) under microwave-assisted reductive amination protocol starting from raspberry ketone and octopamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 h to only 3 h under mild conditions (50 °C at 10 bar). The best catalysts were Pt/C and Rh/C, which led to high conversion and selectivity towards ractopamine:HCl. Different solvents and ketone substrates were also experimented. Acetophenone, cyclohexanone, and 2-butanone reacted at lower H2 pressure (5 bar), and highest selectivity was observed with cyclohexanone (99%). These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures and underline the positive synergy between MW and heterogeneous catalysis.
... Reductive amination is an important and versatile organic reaction that finds extensive applications in sustainable synthetic processes and has been intensively investigated both in both academia and industry [1,2]. Mechanistically, the reaction begins with a condensation step in which the carbonyl compound reacts with ammonia or an amine to form the corresponding imine, followed by reduction of the imine to the alkylamine product [3]. ...
Reductive amination is a powerful tool in sustainable organic synthesis that allows chemists to access a wide range of valuable amine products using renewable feedstocks, mild reaction con-ditions, and with minimal waste generation. Practical applications can be found in various fields, including pharmaceuticals, contributing to greener and more sustainable chemical processes. In this work we present a heterogeneous (Rh and Pt) catalysed protocol for the fast and efficient synthesis of ractopamine hydrochloride (-adrenergic drug) under MW-assisted reductive ami-nation protocol starting from raspberry ketone and octapamine. Microwave (MW) successfully accelerated the hydrogenation reaction and reduced the reaction time from 13 hours to only 3 hours under mild conditions (50°C at 10 bar). The best catalysts were Pt/C and Rh/C, which led to high conversion and selectivity towards ractopamine:HCl. The solvent has a significant effect on the reaction outcome. The replacement of methanol with other solvents had a negative impact on the reaction yield. We also replaced the raspberry ketone with other ketone substrates, especially cyclohexanone. These preliminary experiments may be useful for further process improvements in the synthesis of β-adrenergic agonists and related structures.
... Palladium metal acts as a catalyst, facilitating the reaction by providing a surface for the adsorption of hydrogen atoms and promoting their addition to the substrate molecule [69][70][71]. In addition to hydrogenation reactions, palladium metal is also used in a variety of other reduction reactions, including the reduction of carbonyl compounds and the reductive amination of aldehydes and ketones [72,73]. Overall, the use of palladium metal as a catalyst in reduction reactions offers a highly efficient and effective approach to organic synthesis [65,66]. ...
Introduction
In this work, we have successfully synthesized four types of ionic liquid-mediated Pd nanocatalysts and performed the physiochemical analysis of the developed Pd-based nanocatalysts using a transmission electron microscope (TEM), X-Ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), and atomic absorption spectroscopy (AAS) analysis.
Method
The well-dispersed and fine Pd nanoparticles were recorded in the ILPdNPs-4 catalytic system. We used this catalytic system to reduce a series of aliphatic and aromatic compounds with nitro groups and developed various biologically active amine molecules. In the continuation of the same, we also reduced nitrolactone, which is considered one of the important starting materials for the synthesis of renin inhibitor aliskiren (Tekturna®, and worldwide as Rasilez®).
Result
We also completed the catalyst stability test and recycled the ILPdNPs-4 catalytic system for up to eight runs.
Conclusion
No sign of metal leaching, Pd black formation, and agglomeration was recorded during recycling runs.
... Primary amines are essential raw materials and intermediates in fine chemical industry, playing significant roles in the synthesis of pharmaceuticals, biomolecules, advanced polymers, and agrochemicals (Kim et al., 2013;Cabrero-Antonino et al., 2019;Afanasyev et al., 2020;Irrgang and Kempe, 2020;Murugesan, et al., 2020). Various strategies have been investigated to synthesize primary amines, including reductive amination (Ball et al., 2018;Murugesan et al., 2019;Sukhorukov, 2020), aryl halides amination (Schranck and Tlili, 2018;Wang et al., 2022), nitriles hydrogenation (Garduño and García, 2020;Lévay and Hegedűs, 2018;Chen et al., 2016), olefins hydroamination (Miller et al., 2019;Sengupta et al., 2020), etc. Owing to the application of economical ammonia as well as the accessible reaction engineering, the reductive amination with usage of ammonia as the nitrogen resource represents one of the most cost-effective methods to manufacture primary amines. However, this process usually suffers from the selectivity challenge due to the side reactions including over hydrogenation of imines and reduction of carbonyl compounds to the corresponding alcohols (Chandra et al., 2018;Gallardo-Donaire et al., 2018). ...
Cobalt (Co) as a substitute of noble-metal catalysts shows high catalytic capability for production of the widely used primary amines through the reductive amination. However, the synthesis of Co catalysts usually involves the introduction of organic compounds and the high-temperature pyrolysis, which is complicated and difficult for large-scale applications. Herein, we demonstrated a facile and efficient strategy for the preparation of Co catalysts through the in situ reconstruction of cobalt borate (CoBOx) during the reductive amination, delivering a high catalytic activity for production of benzylamine from benzaldehyde and ammonia. Initially, CoBOx was transformed into Co(OH)2 through the interaction with ammonia and subsequently reduced to Co nanoparticles by H2 under the reaction environments. The in situ generated Co catalysts exhibited a satisfactory activity and selectivity to the target product, which overmatched the commonly used Co/C, Pt or Raney Ni catalysts. We anticipate that such an in situ reconstruction of CoBOx by reactants during the reaction could provide a new approach for the design and optimization of catalysts to produce primary amines.
... The conversion of the alcohol into the corresponding aldehyde is usually the rate-limiting step 30 . Similarly, nitro precursors can be converted into nucleophilic amines prior to the coupling step 31 . Challenges in this reductive amination route include the selective generation of primary amines (if starting from NH 3 as the nitrogenous precursor) and minimizing condensation pathways between the primary amine product and imine intermediates that result in the formation of secondary and tertiary amines. ...
Energy-intensive thermochemical processes within chemical manufacturing are a major contributor to global CO2 emissions. With the increasing push for sustainability, the scientific community is striving to develop renewable energy-powered electrochemical technologies in lieu of CO2-emitting fossil-fuel-driven methods. However, to fully electrify chemical manufacturing, it is imperative to expand the scope of electrosynthetic technologies, particularly through the innovation of reactions involving nitrogen-based reactants. This Review focuses on a rapidly emerging area, namely the formation of C–N bonds through heterogeneous electrocatalysis. The C–N bond motif is found in many fertilizers (such as urea) as well as commodity and fine chemicals (with functional groups such as amines and amides). The ability to generate C–N bonds from reactants such as CO2, NO3– or N2 would provide sustainable alternatives to the thermochemical routes used at present. We start by examining thermochemical, enzymatic and molecular catalytic systems for C–N bond formation, identifying how concepts from these can be translated to heterogeneous electrocatalysis. Next, we discuss successful heterogeneous electrocatalytic systems and highlight promising research directions. Finally, we discuss the remaining questions and knowledge gaps and thus set the trajectory for future advances in heterogeneous electrocatalytic formation of C–N bonds. Reactions that form C–N bonds are key in the synthesis of molecules used in fertilizers, synthetic materials, pharmaceuticals and more. This Review examines the emerging area of heterogeneous electrocatalytic C–N bond formation using abundant starting materials, with the eventual goal of electrifying chemical manufacturing.
... 31 The key organic transformations include reduction of furanic aldehyde functionality by transfer hydrogenation for, e.g. Meerwein−Ponndorf−Verley (MPV) reduction or hydrogenation with molecular hydrogen, 32 acylation, acetalization, oxidation, 33 Knoevenagel and aldol condensations, 34,35 decarbonylation, 36 reductive amination to amines, 37 and Grignard reactions. The −OH group can undergo etherification, esterification, acetalization, hydrogenolysis of the C−O bond, oxidation to aldehyde or acid, and halogenation reactions. ...
... 53 . This is a function of the reaction pathway, which is typically considered to be initial four-electron reduction of the nitro-compound to the primary amine followed by condensation with the carbonyl 52,53 . The secondary amine product of mono- methylation is often more nucleophilic and therefore more reactive towards the carbonyl, leading to bis-methylation. ...
... The discussion on the various catalysts has been focused also on the advantages of the catalysts in terms of recyclability without forgetting to underline some of their drawbacks. For highlights or reviews dealing with other aspects of reductive amination reactions for the synthesis of several kinds of amines, the reader is referred to the works reported in references [7][8][9][10][11][12][13][14][22][23][24]. ...
... As recently highlighted by Sukhorukov [22], the RA of carbonyl derivatives with nitro compounds can viewed as an old reaction because more than 80 years ago Major [39] and Emerson et al. [40,41] reported on the coupling of nitroarenes with aldehydes under catalytic hydrogenation over platinum oxide (PtO2: Adams' catalyst [42]) and Raney Nickel catalyst, respectively. The proposed protocols were generally applicable to both aromatic and aliphatic aldehydes but in most cases low or moderate yields in secondary amines were achieved. ...
Recently, N-substituted anilines have been the object of increasing research interest in the field of organic chemistry due to their role as key intermediates for the synthesis of important compounds such as polymers, dyes, drugs, agrochemicals and pharmaceutical products. Among the various methods reported in literature for the formation of C–N bonds to access secondary anilines, the one-pot reductive amination of aldehydes with nitroarenes is the most interesting procedure, because it allows to obtain diverse N-substituted aryl amines by simple reduction of nitro compounds followed by condensation with aldehydes and subsequent reduction of the imine intermediates. These kinds of tandem reactions are generally catalyzed by transition metal-based catalysts, mainly potentially reusable metal nanoparticles. The rapid growth in the last years in the field of metal-based heterogeneous catalysts for the one-pot reductive amination of aldehydes with nitroarenes demands for a review on the state of the art with a special emphasis on the different kinds of metals used as catalysts and their recyclability features.
