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Base-Free Synthesis of Furfurylamines from Biomass Furans Using Ru Pincer Complexes

Danielle Lobo Justo Pinheiro
Martin Nielsen
Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
Author to whom correspondence should be addressed.
Catalysts 2021, 11(5), 558;
Submission received: 30 March 2021 / Revised: 23 April 2021 / Accepted: 26 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Sustainable and Environmental Catalysis)


We report the first example of employing homogeneous organometal-catalyzed transfer hydrogenation for the selective reductive amination of furfurals to furfurylamines. An efficient, chemoselective, and base-free method is described using Ru-MACHO-BH as catalyst and iPrOH as H donor. The method tolerates a range of substituents affording moderate to excellent yields.

Graphical Abstract

1. Introduction

The development of sustainable techniques to transform biomass into useful compounds is one of the biggest challenges of modern chemistry [1]. The introduction of nitrogen in biomass-derived compounds adds value and expands their industry applicability [2]. Furfurals are aldehydes derived from biomass and are identified as one of the key chemicals produced by the lignocellulosic biorefineries. Around 280 kTon are produced globally per year [3]. Furfurylamines (amines derived from furfurals) present diverse applications in the industry, including the preparation of pharmaceutical compounds such as Furesomide, Furtrethonium, an anti-hepatitis-B, and Barmastine (Figure 1), as well as polymers, antiseptic agents, agrochemicals, pesticides, and synthetic resins [1,2,4].
The synthesis of furfurylamines from furfurals by reductive amination has been investigated using diverse reducing agents and catalysts. Studies involving hydrogen gas, silanes, borohydrides, and formic acid as reductants have been reported in the literature. Hydrogen gas as reductant is an interesting green tool; however, the method needs to operate under pressure of a highly flammable gas, increasing the operating cost. Nevertheless, there are many examples in the literature using H2 as reductant for reductive amination with noble and non-noble metal catalysts such as Ru, Au, Ir, Pt, Ni, Co and Fe [5,6,7,8,9,10,11]. Although silane is obtained from waste residues of the silicon industry, their use is still in stoichiometric amounts, generating excessive amounts of waste [12,13,14]. The use of formic acid as H donor for the reductive amination of furfural was demonstrated as well. Cao and co-workers synthesized N-(furan-2-ylmethyl)aniline in 93% yield from nitrobenzene and furfural using Au/TiO2-R as catalyst at 80 °C for 4 h [15]. Smith Jr and co-workers also employed formic acid as H donor, but used formamide as N source [16]. To the best of our knowledge, the only work involving an alcohol as H donor (iPrOH) for the synthesis of furfurylamines from furfural was reported by Yus [17]. In this work, the reaction between furfural and heptylamine using 20 mol% of NiNPs at 76 °C for 48 h afforded 30% yield of the furfurylamine.
One of the most powerful and robust methods for effective C–N bond formation of amines is the reductive amination of carbonyl compounds. [4,18,19,20,21,22,23,24,25,26,27,28,29,30]. This transformation features compelling advantages, such as simple operating setups, mild reaction conditions, direct use of available substrates, and inexpensive reagents [31]. The reductive amination using transfer hydrogenation for the synthesis of furfurylamines from furfurals is limited, even though this transformation as a synthetic tool is non-toxic, environmentally friendly, does not require flammable gasses, and employs a stable, easy to handle, and inexpensive source of hydrogen [4,32,33,34,35,36,37]. However, transfer hydrogenation catalysts typically require strong bases to be active, which can be detrimental for substrates that are base-sensitive [38]. Therefore, studies applying base-free conditions must be developed to avoid this drawback.
The use of homogenous metal catalysis has demonstrated great reactivity for transfer hydrogenation of carbonyl compounds and has been proven to hold many advantages [38,39,40,41]. In 2018, De Vries reported a base-free transfer hydrogenation of α,β-unsaturated ketones and aldehydes using the PNP pincer complex carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(II) (Ru-MACHO-BH) as catalyst, in the presence of EtOH or iPrOH as H source and showed high activity and selectivity [42]. The amino-based Ru-PNP complexes are also very efficient catalysts for hydrogenation [43,44,45,46,47,48,49] and dehydrogenation [50,51,52,53,54,55,56,57] reactions. The high activity of these Ru PNP complexes in hydrogenations is often attributed to the presence of the Ru–H unit and N–H group [58].
Inspired by these works, we investigated the use of Ru-MACHO [59] (carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)amino]ruthenium(II)) and Ru-MACHO-BH complexes as potential catalysts for the transfer hydrogenation of the reductive amination in this work.

2. Results and Discussion

Our studies commenced with testing Ru-MACHO (1 mol%) as the catalyst for the transfer hydrogenation of the aldimine 1a (Figure S1) in the presence of iPrOH (0.2 M of 1a) as hydrogen source and KOtBu (20 mol%) as additive at 90 °Cfor 3 h (Scheme 1). To our delight, the reaction afforded >99% conversion to furfurylamine 2a. We then set out to evaluate the transfer hydrogenation of 1a using varying catalyst loading, additives, temperatures, and reaction times with the aim of developing a mild protocol for this reaction.
Reducing the reaction time to 15 min, the catalyst loading of Ru-MACHO to 0.5 mol%, and the KOtBu loading to 10 mol% still led to full conversion (Table 1, Entry 3). In fact, after 5 min, 51% was already converted (Entry 4). Changing the additive to NaOH had a detrimental effect, and only 18% conversion was observed. Likewise, lowering the catalyst loading to 0.1 mol% afforded less than 5% conversion. Changing the catalyst to Ru-MACHO-BH showed very low activity within 15 min, both with and without additive (Entries 6 and 7, respectively).
Motivated by these initial positive results, the reductive amination of furfural with aniline was further investigated. Thus, in the presence of 10 mol% KOtBu, 0.5 mol% of Ru-MACHO afforded >99% conversion after 18 h at 90 °C. However, the furfuryl alcohol (FA, 3) appeared as a significant side product in a proportion of 7:3 (2a/3) (Scheme 2). Fortunately, introducing MgSO4 as drying agent led to >99% conversion selectively to the desired product in 3 h (Table 2, Entry 2). Reducing the reaction time to 1 h decreased the selectivity to 93:7. Using Ru-MACHO-BH (0.5 mol%) and MgSO4 but without the basic additive still resulted in 93% conversion after 1 h and with 2a as the sole product by 1H NMR analysis (Entry 3). Increasing the amount of aniline from 1.0 to 1.2 equivalent afforded >99% 2a under otherwise identical conditions (Entry 5). Unfortunately, it was not possible to further reduce the reaction time without compromising the conversion and selectivity (Entries 6–8). Decreasing the amount of Ru-MACHO-BH to 0.25 mol% also led to a low conversion of 11% (Entry 9). Lowering the temperature to 70 °C resulted in practically no conversion (<5%, Entry 10). However, by increasing the temperature to 120 °C, it was possible to achieve exclusively 2a with >99% conversion within 30 min (Entry 11).
A number of drying agents were then tested. Using Na2SO4 at 90 °C afforded >99% conversion in 1 h. However, the selectivity decreased to 97:3 (2a/3) (Entry 12). Decreasing the time further to 15 min maintained the full conversion but led to even lower selectivity, down to 57:42 (2a/3) (Entries 13–15). These observations suggest that the formation of 3 is highly reversible, and that 1a is regenerated from 3 throughout the course of the reaction. Moreover, decreasing the reaction temperature to 70 °C led to merely 17% conversion (Entry 16). Molecular sieves (4 Å) were also evaluated and showed full conversion after 1 h, albeit with slightly lower selectivity (94:6 2a/3) (Entry 17). Decreasing the time further to 15 min maintained the full conversion but also led to lower selectivity, (71:29 2a/3) (Entry 18). The temperature was evaluated, and carrying out the reaction at 70 °C led to 71% conversion and 96:4 (2a/3) of selectivity (Entry 19).
As seen in Figure 2, the levels of 13 differed significantly throughout the course of the reaction, depending on whether Na2SO4 or MgSO4 was employed. Within 15 min, almost all 1a had disappeared and 60% of 2a had already been generated when using Na2SO4. Surprisingly, 35% of 3 was observed at this point. Hereafter, the reaction slowed significantly, and after 30 min, merely 70% of 2a had been produced and 3 had only dropped to 22%. By contrast, with MgSO4 the level of 3 did not exceed 15% throughout the entire course of the reaction, and after 30 min, it was 12%. At this time, there was still an ample amount of 1a (45%) to undergo hydrogenation, and 43% of 2a had been produced. This difference in amount of 1a present during the course of the reaction might explain the superiority of MgSO4 as drying agent after 60 min.
Therefore, although Na2SO4 and molecular sieves demonstrate higher conversion rates than MgSO4, the latter drying agent was chosen due to the higher yield provided after 1 h of reaction time. Therefore, the conditions described in the Entry 5 in Table 2 were defined as standard conditions for the scope.
To assess the general applicability of the Ru-MACHO-BH as a catalyst for the one-pot synthesis of furfurylamines from furfurals and amines, various anilines were evaluated using the standard conditions (Scheme 3). Generally, moderate to excellent yields were obtained. The parent aniline afforded an excellent 93% of isolated product. Comparing the anilines containing either electron-donating or -withdrawing substituents, the latter group showed superior yield. As such, 4-F-C6H4NH2, 4-CF3-C6H4NH2, and 4-aminopyridine generated the best yields of the substituted anilines with 74-95% of isolated products 2hj. The product 2j is analogous to the anti-hepatitis-B compound shown in Figure 1, which demonstrates the direct applicability of the method for the synthesis of pharmacological activity compounds. On the other hand, a donating group (4-CH3-C6H4NH2) afforded lower yield of 61% of 2d. This observation can perhaps be explained by the increased electronic deficiency of the imines when employing 4-CF3-C6H4NH2 as reagent [1]. Various halogens were tested as well and showed moderate to good yields (2b, 2e, 2h). Compounds with substituent in different positions, such as 3-Cl-C6H4NH2 and 2-F-C6H4NH2, showed good tolerance, yielding 60% and 56% of 2c and 2f, respectively. The method was also tested with the secondary amine N-methylaniline, which afforded the tertiary amine 2g in high yield (89%). Unfortunately, no products were observed when employing various primary and secondary alkyl amines (tBuNH2, nHepNH2, Me2NH, morpholine).
5-(hydroxymethyl)furfural (HMF) and 5-methylfurfural are other important biomass-derived furans with industrial applications [60,61]. The furfurylamines derived from HMF are used in the synthesis of biopolymers (polyamides) and pharmaceuticals [4]. The N-(5-methylfurfuryl)aniline is a very important compound used in the synthesis of epoxyisonindoles and bioactive compounds such as anti-bacterial, anti-tuberculosis, anti-tumor, and anti-inflammatory entities [62,63,64,65,66,67,68,69,70]. Therefore, the method is an interesting alternative for the production of these valuable compounds. Hence, we also evaluated this compound as a potential substrate (Scheme 4). The reactions afforded a high yield of 4 (87%) and a moderate yield of 5 (54%).

3. Materials and Methods

3.1. Materials

Most chemicals were purchased from commercial suppliers and used without further purification unless otherwise stated. Hydroxymethylfurfural (HMF, 99%) (Sigma-Aldrich, St. Louis, MO, USA), furfural (99%) (Sigma-Aldrich, St. Louis, MO, USA), 5-methylfurfural (99%, Sigma-Aldrich, St. Louis, MO, USA), KOtBu (99%, Sigma-Aldrich, St. Louis, MO, USA), iPrOH (anhydrous, 99.5%, Sigma-Aldrich, St. Louis, MO, USA), Ru-MACHO (Sigma-Aldrich, St. Louis, MO, USA), and Ru-MACHO-BH (Strem Chemicals, Newburyport, MA, USA) are commercially available and were used without further purification. All reactions dealing with air or moisture-sensitive compounds were performed using standard Schlenk techniques or in an argon-filled glovebox. The 1H and 13C NMR spectra were recorded on a Bruker Avance III 400 MHz spectrometer (Bruker, Billerica, MA, USA) and were referenced to the solvent peak. The software MestReNova version 11.0.0-17609 (Mestrelab, Escondido, CA, USA, 2016) was used for NMR analysis. The software OriginPro 2019 (Academic) (OriginLab, Northampton, MA, USA, 2019) was used for graphic plot. All the products are literature known compounds, and the experimental data (1H and 13C{1H} NMR spectra) fit those reported.

3.2. Methods

3.2.1. Preparation of Aldimine 1a

A mixture of furfural (54 mmol), aniline (54 mmol) and methanol (0.5 M) in the presence of MS (4 Å) was stirred at room temperature for 3 h. After completion of the reaction, the crude mixture was filtered off and evaporated under reduced pressure. The product 1a was obtained as a brown oil, 7.83 g, 85%.

3.2.2. General Procedure for Transfer Hydrogenation of Aldimine 1a Catalyzed by Ru-PNP Complexes

A Schlenk pressure vessel containing catalyst, additive and magnetic bar was sealed and flushed with argon (three times). The solvent and H-donor (i-PrOH) was introduced by a needle and stirred at 90 °C. After 10 min, the aldimine 1a was added to the solution. After a certain reaction time (5–18 h), the reaction was stopped, and the crude was analyzed. The conversion was determined by spectroscopy 1H NMR.

3.2.3. General Procedure for One-Pot Reductive Amination of Furfural

In a Schlenk pressure vessel containing Ru-MACHO-BH (0.5 mol %) and MgSO4 (1.3 mmol), a magnetic stirring bar was added and the vessel was sealed and flushed with argon (three times). During argon flow, 4.5 mL of iPrOH was introduced by a needle and the solution was heated at 90 °C and stirred for 10 min. In a flame-dried screw-cap vial, aniline (1.56 mmol) and furfural (1.3 mmol) were mixed with 2.5 mL of iPrOH (to provide a solution with furfural concentration of 0.18 M) under argon flow. The atmosphere was replaced with argon and the solution was introduced to the Schlenk pressure vessel. The reaction mixture was kept at 90 °C for 1 h. The crude reaction mixture was evaporated under reduced pressure, and the product was obtained after purification through chromatography column (Ethyl acetate/pentane, 90:10). For the optimization process, the method of employing relative conversions as measured by NMR was confirmed with respect to absolute values by a single duplicate test reaction using mesitylene as internal standard.

4. Conclusions

In conclusion, we report the first example of an efficient base free one-pot transfer hydrogenative reductive amination of furfural for the synthesis of furfurylamines under mild conditions, employing low amounts of the commercially available catalyst Ru-MACHO-BH and iPrOH as H donor. The general applicability of the method is demonstrated by the use of furfural and various anilines with different substituents, which afforded yields that varied from moderate to excellent (56–93%). Furthermore, this chemoselective methodology established a high yield (83%) in the synthesis of the furfurylamine derived from HMF and a moderate yield (54%) from N-(5-methylfurfuryl)aniline.

Supplementary Materials

The following are available online at, Table S1: Monitoring the reaction of furfural and aniline using MgSO4 as drying agent. Table S2: Monitoring the reaction of furfural and aniline using Na2SO4 as drying agent. Figure S1: 1H NMR spectrum of 1a (400 MHz, CDCl3), Figure S2: 13C NMR spectrum of 1a (100 MHz, CDCl3), Figure S3: 1H NMR spectrum of 2a (400 MHz, CDCl3), Figure S4: 13C NMR spectrum of 2a (100 MHz, CDCl3), Figure S5: 1H NMR spectrum of 2b (400 MHz, CDCl3), Figure S6: 13C NMR spectrum of 2b (100 MHz, CDCl3), Figure S7: 1H NMR spectrum of 2c (400 MHz, CDCl3), Figure S8: 13C NMR spectrum of 2c (100 MHz, CDCl3), Figure S9: 1H NMR spectrum of 2d (400 MHz, CDCl3), Figure S10: 13C NMR spectrum of 2d (100 MHz, CDCl3), Figure S11: 1H NMR spectrum of 2e (400 MHz, CDCl3), Figure S12: 13C NMR spectrum of 2e (100 MHz, CDCl3), Figure S13: 1H NMR spectrum of 2f (400 MHz, CDCl3), Figure S14: 13C NMR spectrum of 2f (100 MHz, CDCl3), Figure S15: 1H NMR spectrum of 2g (400 MHz, CDCl3), Figure S16: 13C NMR spectrum of 2g (100 MHz, CDCl3), Figure S17: 1H NMR spectrum of 2h (400 MHz, CD3OD), Figure S18: 13C NMR spectrum of 2h (100 MHz, CDCl3), Figure S19: 1H NMR spectrum of 2i (400 MHz, CDCl3), Figure S20: 13C NMR spectrum of 2i (100 MHz, CDCl3), Figure S21: 1H NMR spectrum of 2j (400 MHz, CDCl3), Figure S22: 13C NMR spectrum of 2j (100 MHz, CDCl3), Figure S23: 1H NMR spectrum of 4 (400 MHz, CDCl3), Figure S24: 13C NMR spectrum of 4 (100 MHz, CDCl3), Figure S25: 1H NMR spectrum of 5 (400 MHz, CDCl3), Figure S26: 13C NMR spectrum of 5 (100 MHz, CDCl3).

Author Contributions

D.L.J.P. did the experimental part. M.N. did funding acquisition and project administration. Everything else, from conceptualization to manuscript writing, D.L.J.P. and M.N. did equally. All authors have read and agreed to the published version of the manuscript.


This work was supported by a research grant (19049) from VILLUM FONDEN.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Caetano, J.A.T.; Fernandes, A.C. One-pot synthesis of amines from biomass resources catalyzed by HReO4. Green Chem. 2018, 20, 2494–2498. [Google Scholar] [CrossRef]
  2. Dunbabin, A.; Subrizi, F.; Ward, J.M.; Sheppard, T.D.; Hailes, H.C. Furfurylamines from biomass: Transaminase catalysed upgrading of furfurals. Green Chem. 2017, 19, 397–404. [Google Scholar] [CrossRef] [Green Version]
  3. Mariscal, R.; Maireles-Torres, P.; Ojeda, M.; Sádabaa, I.; Granados, M.L. Furfural: A renewable and versatile platform molecule for the synthesis of chemicals and fuels. Energy Environ. Sci. 2016, 9, 1144–1189. [Google Scholar] [CrossRef]
  4. He, J.; Chen, L.; Liu, S.; Song, K.; Yang, S.; Riisager, A. Sustainable access to renewable N-containing chemicals from reductive amination of biomass-derived platform compounds. Green Chem. 2020, 22, 6714–6747. [Google Scholar] [CrossRef]
  5. Chieffi, G.; Braun, M.; Esposito, D. Continuous reductive amination of biomass-derived molecules over carbonized filter paper-supported FeNi alloy. ChemSusChem 2015, 8, 3590–3594. [Google Scholar] [CrossRef] [Green Version]
  6. Deng, D.; Kita, Y.; Kamata, K.; Hara, M. Low-Temperature Reductive Amination of Carbonyl Compounds over Ru Deposited on Nb2O5 · nH2O. ACS Sustain. Chem. Eng. 2019, 7, 4692–4698. [Google Scholar] [CrossRef]
  7. Laroche, B.; Ishitani, H.; Kobayashi, S. Direct Reductive Amination of Carbonyl Compounds with H2 Using Heterogeneous Catalysts in Continuous Flow as an Alternative to N-Alkylation with Alkyl Halides. Adv. Synth. Catal. 2018, 360, 4699–4704. [Google Scholar] [CrossRef]
  8. Gould, N.S.; Landfield, H.; Dinkelacker, B.; Brady, C.; Yang, X.; Xu, B. Selectivity Control in Catalytic Reductive Amination of Furfural to Furfurylamine on Supported Catalysts. ChemCatChem 2020, 12, 2106–2115. [Google Scholar] [CrossRef]
  9. Murugesan, K.; Senthamarai, T.; Chandrashekhar, V.G.; Natte, K.; Kamer, P.C.J.; Beller, M.; Jagadeesh, R.V. Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines. Chem. Soc. Rev. 2020, 49, 6273–6328. [Google Scholar] [CrossRef] [PubMed]
  10. Zhou, K.; Chen, B.; Zhou, X.; Kang, S.; Xu, Y.; Wei, J. Selective Synthesis of Furfurylamine by Reductive Amination of Furfural over Raney Cobalt. ChemCatChem 2019, 11, 5562–5569. [Google Scholar] [CrossRef]
  11. Dong, C.; Wang, H.; Du, H.; Peng, J.; Cai, Y.; Guo, S.; Zhang, J.; Samart, C.; Ding, M. Ru/HZSM-5 as an efficient and recyclable catalyst for reductive amination of furfural to furfurylamine. Mol. Catal. 2020, 482, 110755. [Google Scholar] [CrossRef]
  12. Carrillo, A.I.; Llanes, P.; Pericàs, M.A. A versatile, immobilized gold catalyst for the reductive amination of aldehydes in batch and flow. React. Chem. Eng. 2018, 3, 714–721. [Google Scholar] [CrossRef]
  13. Maya, R.J.; Poulose, S.; John, J.; Varma, R.L. Direct Reductive Amination of Aldehydes via Environmentally Benign Bentonite-Gold Nanohybrid Catalysis. Adv.Synth. Catal. 2017, 359, 1177–1184. [Google Scholar] [CrossRef]
  14. Mirza-Aghayan, M.; Kalantari, M.; Boukherroub, R. Palladium oxide nanoparticles supported on graphene oxide: A convenient heterogeneous catalyst for reduction of various carbonyl compounds using triethylsilane. Appl. Organomet. Chem. 2019, 33, 1–11. [Google Scholar] [CrossRef]
  15. Zhang, Q.; Li, S.; Zhu, M.; Liu, Y.; He, H.; Cao, Y. Direct reductive amination of aldehydes with nitroarenes using bio-renewable formic acid as a hydrogen source. Green Chem. 2016, 18, 2507–2513. [Google Scholar] [CrossRef]
  16. Li, H.; Guo, H.; Su, Y.; Hiraga, Y.; Fang, Z.; Watanabe, M.; Lee, R.; Smith, R.L., Jr.; Hensen, E.J.M. N-formyl-stabilizing quasi-catalytic species afford rapid and selective solvent-free amination of biomass-derived feedstocks. Nat. Commun. 2019, 10, 699. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Guillena, G.; Ramo, D.J.; Yus, M. Hydrogen Autotransfer in the N-Alkylation of Amines and Related Compounds using Alcohols and Amines as Electrophiles. Chem. Rev. 2010, 110, 1611–1641. [Google Scholar] [CrossRef] [PubMed]
  18. Irrgang, T.; Kempe, R. Transition-metal-catalyzed reductive amination employing hydrogen. Chem. Rev. 2020, 120, 9583–9674. [Google Scholar] [CrossRef] [PubMed]
  19. Wang, Y.; Furukawa, S.; Fu, X.; Yan, N. Organonitrogen chemicals from oxygen-containing feedstock over heterogeneous catalysts. ACS Catal. 2020, 10, 311–335. [Google Scholar] [CrossRef]
  20. Saberi, A.A. Recent advances in percolation theory and its applications. Phys. Rep. 2015, 578, 1–32. [Google Scholar] [CrossRef] [Green Version]
  21. Chen, W.; Sun, Y.; Du, J.; Si, Z.; Tang, X.; Zeng, X.; Lin, L.; Liu, S.; Lei, T. Preparation of 5-(Aminomethyl)-2-furanmethanol by direct reductive amination of 5-Hydroxymethylfurfural with aqueous ammonia over the Ni/SBA-15 catalyst. J. Chem. Technol. Biotechnol. 2018, 93, 3028–3034. [Google Scholar] [CrossRef]
  22. Nuzhdin, A.L.; Bukhtiyarova, M.V.; Bukhtiyarova, G.A. Cu-Al mixed oxide derived from layered double hydroxide as an efficient catalyst for continuous-flow reductive amination of aromatic aldehydes. J. Chem. Technol. Biotechnol. 2020, 95, 3292–3299. [Google Scholar] [CrossRef]
  23. Nuzhdin, A.L.; Simonov, P.A.; Bukhtiyarova, G.A.; Eltsov, I.V.; Bukhtiyarov, V.I. Reductive amination of 5-acetoxymethylfurfural over Pt/Al2O3 catalyst in a flow reactor. Mol. Catal. 2021, 499, 111297. [Google Scholar] [CrossRef]
  24. Galkin, K.I.; Ananikov, V.P. The Increasing Value of Biomass: Moving From C6 Carbohydrates to Multifunctionalized Building Blocks via 5-(hydroxymethyl)furfural. ChemistryOpen 2020, 9, 1135–1148. [Google Scholar] [CrossRef]
  25. Lancien, A.; Wojcieszak, R.; Cuvelier, E.; Duban, M.; Dhulster, P.; Paul, S.; Dumeignil, F.; Froidevaux, R.; Heuson, E. Hybrid Conversion of 5-Hydroxymethylfurfural to 5-Aminomethyl-2-furancarboxylic acid: Toward New Bio-sourced Polymers. ChemCatChem 2021, 13, 247–259. [Google Scholar] [CrossRef]
  26. Yang, Z.Y.; Hao, Y.C.; Hu, S.Q.; Zong, M.H.; Chen, Q.; Li, N. Direct Reductive Amination of Biobased Furans to N-Substituted Furfurylamines by Engineered Reductive Aminase. Adv. Synth. Catal. 2021, 363, 1033–1037. [Google Scholar] [CrossRef]
  27. García-Ortiz, A.; Vidal, J.D.; Climent, M.J.; Concepción, P.; Corma, A.; Iborra, S. Chemicals from Biomass: Selective Synthesis of N-Substituted Furfuryl Amines by the One-Pot Direct Reductive Amination of Furanic Aldehydes. ACS Sustain. Chem. Eng. 2019, 7, 6243–6250. [Google Scholar] [CrossRef]
  28. Wei, D.; Bruneau-Voisine, A.; Dubois, M.; Bastin, S.; Sortais, J.B. Manganese-Catalyzed Transfer Hydrogenation of Aldimines. ChemCatChem 2019, 11, 5256–5259. [Google Scholar] [CrossRef]
  29. Tanaka, K.; Miki, T.; Murata, K.; Yamaguchi, A.; Kayaki, Y.; Kuwata, S.; Ikariya, T.; Watanabe, M. Reductive amination of ketonic compounds catalyzed by Cp*Ir(III) complexes bearing a picolinamidato ligand. J. Org. Chem. 2019, 84, 10962–10977. [Google Scholar] [CrossRef]
  30. Yang, M.L.; Wu, Y.X.; Liu, Y.; Qiu, J.J.; Liu, C.M. A novel bio-based AB2 monomer for preparing hyperbranched polyamides derived from levulinic acid and furfurylamine. Polym. Chem. 2019, 10, 6217–6226. [Google Scholar] [CrossRef]
  31. Chatterjee, M.; Ishizaka, T.; Kawanami, H. Reductive amination of furfural to furfurylamine using aqueous ammonia solution and molecular hydrogen: An environmentally friendly approach. Green Chem. 2016, 18, 487–496. [Google Scholar] [CrossRef]
  32. Piccirilli, L.; Pinheiro, D.L.J.; Nielsen, M. Recent progress with pincer transition metal catalysts for sustainability. Catalysts 2020, 10, 773. [Google Scholar] [CrossRef]
  33. Wang, D.; Astruc, D. The Golden Age of Transfer Hydrogenation. Chem. Rev. 2015, 115, 6621–6686. [Google Scholar] [CrossRef]
  34. Wang, C.; Wu, X.; Xiao, J. Broader, greener, and more efficient: Recent advances in asymmetric transfer hydrogenation. Chem. Asian J. 2008, 3, 1750–1770. [Google Scholar] [CrossRef]
  35. Farrar-tobar, R.A.; Dell’Acqua, A.; Tin, S.; de Vries, J.G. Metal-catalysed selective transfer hydrogenation of α,β-unsaturated carbonyl compounds to allylic alcohols. Green Chem. 2020, 22, 3323–3357. [Google Scholar] [CrossRef]
  36. Clapham, S.E.; Hadzovic, A.; Morris, R.H. Mechanisms of the H2-hydrogenation and transfer hydrogenation of polar bonds catalyzed by ruthenium hydride complexes. Coord. Chem. Rev. 2004, 248, 2201–2237. [Google Scholar] [CrossRef]
  37. Werkmeister, S.; Neumann, J.; Junge, K.; Beller, M. Pincer-Type Complexes for Catalytic (De)Hydrogenation and Transfer (De)Hydrogenation Reactions: Recent Progress. Chem. Eur. J. 2015, 21, 12226–12250. [Google Scholar] [CrossRef]
  38. Farrar-Tobar, R.A.; Wozniak, B.; Savini, A.; Hinze, S.; Tin, S.; de Vries, J.G. Base-Free Iron Catalyzed Transfer Hydrogenation of Esters Using EtOH as Hydrogen Source. Angew. Chem. Int. Ed. 2019, 58, 1129–1133. [Google Scholar] [CrossRef] [PubMed]
  39. Clarke, Z.E.; Maragh, P.T.; Dasgupta, T.P.; Gusev, D.G.; Lough, A.J.; Abdur-Rashid, K. A family of active iridium catalysts for transfer hydrogenation of ketones. Organometallics 2006, 25, 4113–4117. [Google Scholar] [CrossRef]
  40. Castellanos-blanco, N.; Arévalo, A.; García, J.J. Nickel-catalyzed transfer hydrogenation of ketones using ethanol as a solvent and a hydrogen donor. Dalt. Trans. 2016, 45, 13604–13614. [Google Scholar] [CrossRef]
  41. Aboo, A.H.; Begum, R.; Zhao, L.; Farooqi, Z.H.; Xiao, J. Methanol as hydrogen source: Chemoselective transfer hydrogena- tion of α,β -unsaturated ketones with a rhodacycle. Chin. J. Catal. 2019, 40, 1795–1799. [Google Scholar] [CrossRef]
  42. Farrar-tobar, R.A.; Wei, Z.; Jiao, H.; Hinze, S.; Vries, J.G. De Selective Base-free Transfer Hydrogenation of α,β-Unsaturated Carbonyl Compounds using iPrOH or EtOH as Hydrogen Source. Chem. Eur.J. 2018, 24, 2725–2734. [Google Scholar] [CrossRef]
  43. Padilla, R.; Koranchalil, S.; Nielsen, M. Efficient and selective catalytic hydrogenation of furanic aldehydes using well defined Ru and Ir pincer complexes. Green Chem. 2020, 22, 6767–6772. [Google Scholar] [CrossRef]
  44. Padilla, R.; Nielsen, M.; Jørgensen, M.S.B. Efficient catalytic hydrogenation of alkyl levulinates to γ-valerolactone. Green Chem. 2019, 21, 5195–5200. [Google Scholar] [CrossRef]
  45. Garbe, M.; Wei, Z.; Tannert, B.; Spannenberg, A.; Jiao, H.; Bachmann, S.; Scalone, M.; Junge, K.; Beller, M. Enantioselective Hydrogenation of Ketones using Different Metal Complexes with a Chiral PNP Pincer Ligand. Adv. Synth. Catal. 2019, 361, 1913–1920. [Google Scholar] [CrossRef]
  46. Guan, C.; Pan, Y.; Ang, E.P.L.; Hu, J.; Yao, C.; Huang, M.H.; Li, H.; Lai, Z.; Huang, K.W. Conversion of CO2 from air into formate using amines and phosphorus-nitrogen PN3P-Ru(ii) pincer complexes. Green Chem. 2018, 20, 4201–4205. [Google Scholar] [CrossRef]
  47. Neumann, J.; Bornschein, C.; Jiao, H.; Junge, K.; Beller, M. Hydrogenation of Aliphatic and Aromatic Nitriles Using a Defined Ruthenium PNP Pincer Catalyst. Eur. J. Org. Chem. 2015, 2015, 5944–5948. [Google Scholar] [CrossRef]
  48. Filonenko, G.A.; Van Putten, R.; Schulpen, E.N.; Hensen, E.J.M.; Pidko, E.A. Highly efficient reversible hydrogenation of carbon dioxide to formates using a ruthenium PNP-pincer catalyst. ChemCatChem 2014, 6, 1526–1530. [Google Scholar] [CrossRef]
  49. Filonenko, G.A.; Hensen, E.J.M.; Pidko, E.A. Mechanism of CO2 hydrogenation to formates by homogeneous Ru-PNP pincer catalyst: From a theoretical description to performance optimization. Catal. Sci. Technol. 2014, 4, 3474–3485. [Google Scholar] [CrossRef] [Green Version]
  50. Oldenhuis, N.J.; Dong, V.M.; Guan, Z. Catalytic acceptorless dehydrogenations: Ru-Macho catalyzed construction of amides and imines. Tetrahedron 2014, 70, 4213–4218. [Google Scholar] [CrossRef] [Green Version]
  51. Agapova, A.; Alberico, E.; Kammer, A.; Junge, H.; Beller, M. Catalytic Dehydrogenation of Formic Acid with Ruthenium-PNP-Pincer Complexes: Comparing N-Methylated and NH-Ligands. ChemCatChem 2019, 11, 1910–1914. [Google Scholar] [CrossRef] [Green Version]
  52. Bertoli, M.; Choualeb, A.; Lough, A.J.; Moore, B.; Spasyuk, D.; Gusev, D.G. Osmium and ruthenium catalysts for dehydrogenation of alcohols. Organometallics 2011, 30, 3479–3482. [Google Scholar] [CrossRef]
  53. Alberico, E.; Lennox, A.J.J.; Vogt, L.K.; Jiao, H.; Baumann, W.; Drexler, H.J.; Nielsen, M.; Spannenberg, A.; Checinski, M.P.; Junge, H.; et al. Unravelling the Mechanism of Basic Aqueous Methanol Dehydrogenation Catalyzed by Ru-PNP Pincer Complexes. J. Am. Chem. Soc. 2016, 138, 14890–14904. [Google Scholar] [CrossRef] [Green Version]
  54. Nielsen, M.; Alberico, E.; Baumann, W.; Drexler, H.J.; Junge, H.; Gladiali, S.; Beller, M. Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide. Nature 2013, 495, 85–89. [Google Scholar] [CrossRef]
  55. Sponholz, P.; Mellmann, D.; Cordes, C.; Alsabeh, P.G.; Li, B.; Li, Y.; Nielsen, M.; Junge, H.; Dixneuf, P.; Beller, M. Efficient and Selective Hydrogen Generation from Bioethanol using Ruthenium Pincer-type Complexes. ChemSusChem 2014, 7, 2419–2422. [Google Scholar] [CrossRef]
  56. Li, Y.; Nielsen, M.; Li, B.; Dixneuf, P.H.; Junge, H.; Beller, M. Ruthenium-catalyzed hydrogen generation from glycerol and selective synthesis of lactic acid. Green Chem. 2015, 17, 193–198. [Google Scholar] [CrossRef]
  57. Nielsen, M.; Junge, H.; Kammer, A.; Beller, M. Towards a green process for bulk-scale synthesis of ethyl acetate: Efficient acceptorless dehydrogenation of ethanol. Angew. Chem. Int. Ed. 2012, 51, 5711–5713. [Google Scholar] [CrossRef]
  58. Dub, P.A.; Gordon, J.C. The role of the metal-bound N–H functionality in Noyori-type molecular catalysts. Nat. Rev. Chem. 2018, 2, 396–408. [Google Scholar] [CrossRef]
  59. Kuriyama, W.; Matsumoto, T.; Ogata, O.; Ino, Y.; Aoki, K.; Tanaka, S.; Ishida, K.; Kobayashi, T.; Sayo, N.; Saito, T. Catalytic Hydrogenation of Esters. Development of an Efficient Catalyst and Processes for Synthesising (R)-1,2-Propanediol and 2-(l-Menthoxy)ethanol. Org. Process Res. Dev. 2012, 16, 166–171. [Google Scholar] [CrossRef]
  60. Hu, L.; Lin, L.; Wu, Z.; Zhou, S.; Liu, S. Recent advances in catalytic transformation of biomass-derived 5-hydroxymethylfurfural into the innovative fuels and chemicals. Renew. Sustain. Energy Rev. 2017, 74, 230–257. [Google Scholar] [CrossRef]
  61. Hou, Q.; Qi, X.; Zhen, M.; Qian, H.; Nie, Y.; Bai, C.; Zhang, S.; Bai, X.; Ju, M. Biorefinery roadmap based on catalytic production and upgrading 5-hydroxymethylfurfural. Green Chem. 2021, 23, 119–231. [Google Scholar] [CrossRef]
  62. Xiao, J.; Jin, Q.; Yang, J.; Xiong, L.; Qiu, J.; Jiang, J.; Peng, Y.; Li, T.; Qiu, Z.; Yang, W. Catalytic Synthesis of N-(5-Methylfurfuryl)aniline from Bio-Derived Carbohydrates. Asian J. Org. Chem. 2019, 8, 328–334. [Google Scholar] [CrossRef]
  63. Zubkov, F.I.; Nikitina, E.V.; Galeev, T.R.; Zaytsev, V.P.; Khrustalev, V.N.; Novikov, R.A.; Orlova, D.N.; Varlamov, A.V. General synthetic approach towards annelated 3a,6-epoxyisoindoles by tandem acylation/IMDAF reaction of furylazaheterocycles. Scope and limitations. Tetrahedron 2014, 70, 1659–1690. [Google Scholar] [CrossRef]
  64. Wu, J.; Darcel, C. Iron-Catalyzed Hydrogen Transfer Reduction of Nitroarenes with Alcohols: Synthesis of Imines and Aza Heterocycles. J. Org. Chem. 2021, 86, 1023–1036. [Google Scholar] [CrossRef]
  65. Ge, C.; Sang, X.; Yao, W.; Zhang, L.; Wang, D. Unsymmetrical indazolyl-pyridinyl-triazole ligand-promoted highly active iridium complexes supported on hydrotalcite and its catalytic application in water. Green Chem. 2018, 20, 1805–1812. [Google Scholar] [CrossRef]
  66. Weickmann, D.; Frey, W.; Plietker, B. Synchronizing steric and electronic effects in {RuII(NNNN,P)} complexes: The catalytic dehydrative alkylation of anilines by using alcohols as a case study. Chem. Eur. J. 2013, 19, 2741–2748. [Google Scholar] [CrossRef]
  67. Iovel, I.; Golomba, L.; Popelis, J.; Grinberga, S.; Lukevics, E. Synthesis and hydrosilylation of furan and thiophene N- methylenefluoroanilines in the presence of Pd(I) complex. Chem. Heterocycl. Compd. 2005, 41, 1112–1118. [Google Scholar] [CrossRef]
  68. Lim, C.H.; Kudisch, M.; Liu, B.; Miyake, G.M. C-N Cross-Coupling via Photoexcitation of Nickel-Amine Complexes. J. Am. Chem. Soc. 2018, 140, 7667–7673. [Google Scholar] [CrossRef]
  69. Ware, R.W.; Hinkley, L.A.; Hardeman, K.P.; Jenks, M.G. Substituted Quinoline and Quinazoline Inhibitors of Quinone Reductase 2. U.S. Patent Application No. WO2006034235A3, 6 April 2006. [Google Scholar]
  70. Nuzhdin, A.L.; Bukhtiyarova, M.V.; Bukhtiyarov, V.I. Two-Step One-Pot Reductive Amination of Furanic Aldehydes Using CuAlOx Catalyst in a Flow Reactor. Molecules 2020, 25, 4771. [Google Scholar] [CrossRef]
Figure 1. Pharmaceutical compounds containing furfurylamines.
Figure 1. Pharmaceutical compounds containing furfurylamines.
Catalysts 11 00558 g001
Scheme 1. (a) Ru-PNP catalysts used in this work. (b) Transfer hydrogenation of aldimine using Ru-MACHO. [a] Measured by 1H NMR spectroscopy analysis of the crude reaction mixture.
Scheme 1. (a) Ru-PNP catalysts used in this work. (b) Transfer hydrogenation of aldimine using Ru-MACHO. [a] Measured by 1H NMR spectroscopy analysis of the crude reaction mixture.
Catalysts 11 00558 sch001
Scheme 2. Reductive amination between furfural and aniline.
Scheme 2. Reductive amination between furfural and aniline.
Catalysts 11 00558 sch002
Figure 2. Monitoring the reaction of furfural with aniline using either MgSO4 as drying agent (a) or Na2SO4 as drying agent (b). Reactions were carried out using 1.3 mmol of furfural, 1.2 equivalent aniline, and 1.3 mmol of drying agent in 7 mL iPrOH.
Figure 2. Monitoring the reaction of furfural with aniline using either MgSO4 as drying agent (a) or Na2SO4 as drying agent (b). Reactions were carried out using 1.3 mmol of furfural, 1.2 equivalent aniline, and 1.3 mmol of drying agent in 7 mL iPrOH.
Catalysts 11 00558 g002
Scheme 3. One-pot synthesis of furfurylamines catalyzed by Ru-MACHO-BH. Reactions were carried out using 1.3 mmol of furfural, 1.56 mmol of aniline, and 1.3 mmol of MgSO4 in 7 mL iPrOH. All yields are isolated.
Scheme 3. One-pot synthesis of furfurylamines catalyzed by Ru-MACHO-BH. Reactions were carried out using 1.3 mmol of furfural, 1.56 mmol of aniline, and 1.3 mmol of MgSO4 in 7 mL iPrOH. All yields are isolated.
Catalysts 11 00558 sch003
Scheme 4. One-pot synthesis of furfurylamines catalyzed by Ru-MACHO-BH. Reactions were carried out using 1.3 mmol of furfural, 1.56 mmol of aniline and 1.3 mmol of MgSO4 in 7 mL of iPrOH. [a] Isolated yield.
Scheme 4. One-pot synthesis of furfurylamines catalyzed by Ru-MACHO-BH. Reactions were carried out using 1.3 mmol of furfural, 1.56 mmol of aniline and 1.3 mmol of MgSO4 in 7 mL of iPrOH. [a] Isolated yield.
Catalysts 11 00558 sch004
Table 1. Transfer hydrogenation of aldimines: Initial studies.
Table 1. Transfer hydrogenation of aldimines: Initial studies.
Entry aCatalyst (mol%)Additive bTimeConv. c (%)
1Ru-MACHO (0.5)KOtBu1 h>99
2Ru-MACHO (0.5)KOtBu 30 min>99
3Ru-MACHO (0.5)KOtBu15 min>99
4Ru-MACHO (0.5)KOtBu5 min51
5Ru-MACHO (0.5)NaOH15 min18
6Ru-MACHO (0.1)KOtBu15 min<5
7Ru-MACHO-BH (0.5)-15 min<5
a Reactions were carried out using 1.3 mmol of furfural and aniline in 7 mL iPrOH at 90 °C. b 10 mol% additive used. c Measured by 1H NMR spectroscopy analysis of the crude reaction mixture.
Table 2. One-pot synthesis of furfurylamines: Optimization.
Table 2. One-pot synthesis of furfurylamines: Optimization.
Entry aCatalyst (mol%)Additive bTemperature (°C)TimeConversion c (%)2a c (%)3 c (%)
1Ru-MACHO (0.5)KOtBu9018 h>997030
2Ru-MACHO (0.5)KOtBu + MgSO4903 h>99>99-
3Ru-MACHO (0.5)KOtBu + MgSO4901 h>99937
4Ru-MACHO-BH (0.5)MgSO4901 h93>99-
5 dRu-MACHO-BH (0.5)MgSO4901 h>99>99-
6 dRu-MACHO-BH (0.5)MgSO49045 min758614
7 dRu-MACHO-BH (0.5)MgSO49030 min307327
8 dRu-MACHO-BH (0.5)-9030 min155248
9 dRu-MACHO-BH (0.25)MgSO4901 h11->99
10 dRu-MACHO-BH (0.5)MgSO4701 h<5--
11 dRu-MACHO-BH (0.5)MgSO412030 min>99>99-
12 dRu-MACHO-BH (0.5)Na2SO4901 h>99973
13 dRu-MACHO-BH (0.5)Na2SO49045 min>999010
14 dRu-MACHO-BH (0.5)Na2SO49030 min>997624
15 dRu-MACHO-BH (0.5)Na2SO49015 min>995742
16 dRu-MACHO-BH (0.5)Na2SO4701 h177228
17 dRu-MACHO-BH (0.5)MS 4 Å901 h>99946
18 dRu-MACHO-BH (0.5)MS 4 Å9015 min>997129
19 dRu-MACHO-BH (0.5)MS 4 Å701 h71964
a Reactions were carried out using 1.3 mmol of furfural, aniline, and 1.3 mmol of drying agent in 7 mL iPrOH. b 10 mol% of KOtBu used. c Measured by 1H NMR spectroscopy analysis of the crude reaction mixture. d Reactions were carried out using 1.2 equivalent of aniline. MS = Molecular sieves.
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Pinheiro, D.L.J.; Nielsen, M. Base-Free Synthesis of Furfurylamines from Biomass Furans Using Ru Pincer Complexes. Catalysts 2021, 11, 558.

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Pinheiro DLJ, Nielsen M. Base-Free Synthesis of Furfurylamines from Biomass Furans Using Ru Pincer Complexes. Catalysts. 2021; 11(5):558.

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Pinheiro, Danielle Lobo Justo, and Martin Nielsen. 2021. "Base-Free Synthesis of Furfurylamines from Biomass Furans Using Ru Pincer Complexes" Catalysts 11, no. 5: 558.

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