Selective reduction of nitroarenes using Ru/C and CaH₂

Abstract

Herein, we report an efficient and highly selective method for the reduction of aromatic, heteroaromatic and halonitro compounds using the readily available and cost-effective Ru/C as a catalyst along with unconventional CaH₂ as a source of hydride. In most cases the corresponding anilines can be obtained by simple filtration without further purification. The use of 2-MeTHF and the simple operational work-up constitute a valid alternative to previous methodologies.

---

Introduction

The reduction of nitro compounds to the corresponding amines has been a matter of investigation since nitrobenzene was reduced to aniline using stoichiometric amounts of sodium sulfide more than a century ago.¹ Since then, nitro compounds have been extensively used as starting materials for the synthesis of primary amines.² The relevance of this transformation lies in the importance of amines in the synthesis of pharmaceuticals, agrochemicals and dyes, as well as intermediates or building blocks for the fine chemicals industry.³ Among the several methodologies developed for this pivotal transformation, including homogeneous catalysis,⁴ metal-free reductions,⁵ water–gas shift reaction,⁶ and the use of nanoparticles,⁷ the development of heterogeneous catalytic systems constitutes one of the most important approaches especially on an industrial scale,⁸ probably because of the simple work-up procedure, which consists of filtration and concentration to isolate the product. Typical heterogeneous catalysts are noble and non-noble metals such as palladium, platinum, ruthenium, iron, copper, manganese, nickel etc. These catalysts are used in the presence of molecular hydrogen (H₂) or a hydrogen donor in catalytic (transfer) hydrogenation.⁹ Another approach is the use of hydride species that under aqueous or protic solvent conditions hydrolyze to give H₂. Remarkably, despite the great advances in the field and the excellent contributions from different research groups, the main issue related to the use of heterogeneous catalysts is the chemoselective reduction of nitro groups in the presence of other reducible functionalities or nitro compounds containing heteroatoms.¹⁰ Thus, the development of new and highly chemoselective methodologies is of great relevance.¹¹ Likewise, dehalogenation of halonitroaromatic compounds is commonly observed as a side reaction during the reduction reaction.¹²

Among the available hydrides, aluminum hydride (LiAlH₄) is a very reactive non-selective nitro reducing agent able to reduce other functionalities such as amides, nitriles and aldehydes among others, resulting in an obvious limitation for a more extended use.¹³ Moreover, LiAlH₄ is a highly corrosive and flammable solid, and a tedious work-up is associated with its use. The presence of water results in the release of hydrogen, which can be ignited by the heat from the exothermic reaction.¹⁴ In contrast, boron hydrides and silanes have been pointed out as non-reactive reagents.¹⁵ On the other hand, sodium borohydride (NaBH₄) is probably the most widely used reagent for this transformation,¹⁶ since its reactivity is enhanced by supported metal-based catalysts such as nickel, copper, and cobalt, and also palladium and platinum on carbon.¹⁷

Interestingly, calcium hydride (CaH₂), which is normally used as a drying agent,¹⁸ has been scarcely exploited as a reducing agent. Only few reports exist about its utility as a hydride source for reduction reactions, despite its being air-stable, inexpensive, and easy to handle and by-products, such as calcium hydroxide (Ca(OH)₂), derived from its use are non-toxic and can be separated by simple filtration.¹⁹ In 2005, the group of Okamoto reported the reduction of ketones and imines with the system CaH₂/ZnX₂.²⁰ Two years later, in 2007, the same group expanded this work with the system ZnX₂/CaH₂/R3SiCl for the reduction of a variety of carbonyl compounds.²¹ In 2015 the group of Métay and Lemaire reported the reductive alkylation and reductive amination of carbonyl compounds using CaH₂ but this time in combination with supported heterogeneous catalysts of Pd/C and Pt/C respectively.²² Based on these reports and as part of our continuing interest in the reduction of organic functionalities,²³ we decided to explore the suitability of this hydride for the reduction of nitroarenes. Herein we report the highly selective reduction of aromatic and heteroaromatic nitro compounds using Ru/C and CaH₂.

Results and discussion

In our seminal attempts, we studied the reduction of p-nitrophenol as a benchmark substrate. p-Nitrophenol is a toxic compound;²⁴ nevertheless, it is a key intermediate in the synthesis of paracetamol (N-acetyl-4-aminophenol),²⁵ one of the most prescribed drugs in the world, but also in the synthesis of dyes and agrochemicals.²⁶ Using CaH₂ and tetrahydrofuran (THF) as solvent, several supported heterogeneous catalysts were screened (Table 1).

Table 1 Screening of heterogeneous catalysts for the reduction of p-nitrophenol as benchmark substrate^a

Entry	Catalyst	Conversion (%)	1a (%)	Yield (%)
a Reaction conditions: 0.5 mmol substrate, [M] (5 mol%) and CaH2 (10 mmol) in THF (4.0 mL) at 100 °C for 20 hours in a sealed tube. Conversions, yields and ratios were determined by GC using decane as internal standard.
1	Pt/C	99	<1	69
2	Pd/C	99	<1	60
3	Rh/C	95	5	39
4	Ru/C	99	1	99
5	Pt/Al2O3	95	5	81
6	Pd/Al2O3	98	2	50
7	Rh/Al2O3	99	<1	62
8	Ru/Al2O3	21	78	12
9	Pt/SiO2	23	76	13
10	Pd/SiO2	43	56	4

---

From these data, we observed that heterogeneous catalysts supported on carbon and alumina were the best systems in terms of conversion and yields (entries 1–7), except for Ru/Al (entry 8) with similar values to those for catalysts supported on silica (entries 9 and 10). On the other hand, it is well known that the type of metal employed in the reaction is the most important parameter regarding the activity and selectivity. Thus, it is accepted that, at least in the hydrogenation of nitrobenzenes, the activity of unsupported and carbon-supported metals is as follows: Pt > Pd > Rh > Ir > Os > Ru.²⁷ In contrast to this accepted tendency, the highest activity of carbon-supported catalysts was found to be for Ru on carbon, with 99% conversion and 99% yield (entry 4). However, for alumina-supported catalysts, the tendency was as expected with Pt on alumina giving a significant yield of 81% (entry 5). Although ruthenium belongs to the platinum series, it is undoubtedly the most cost-effective metal amongst the precious metals. No less important is the fact that the order of selectivity in the reduction of halonitroarenes is Ru > Pt > Rh > Pd, which could be of great interest for the reduction of these substrates.²⁸ Encouraged by this result, and as part of our interest in the development of sustainable methodologies,²⁹ we decided to explore the use of 2-methyltetrahydrofuran (2-MeTHF) as an environmentally friendly alternative solvent³⁰ to the more widely used THF and in line with the principles of Green Chemistry.³¹ Considering that solvents are the main source of waste in chemical processes,³² the introduction of eco-friendly alternatives has become an area of intense investigation.³³ In this context, 2-MeTHF can be obtained from biomass resources and is abiotically degraded by sunlight and air.³⁴ To our delight excellent conversion and yield were also obtained; therefore we selected it as a reaction medium for this reaction, although an additional screening of solvents was performed. In toluene and ethanol, the reaction did not work. In N-methylpyrrolidone and acetonitrile, 75% yield of the corresponding amine was obtained, whereas in DMF the yield was 90%. Thus, the reaction is still active in other solvents but affording low yields. The use of DMF is not attractive since it is toxic, cannot be as easily removed as THF or 2-MeTHF, and a more tedious work-up is necessary. Control experiments without catalyst or without CaH₂ were performed. In addition, although great efforts have been developed to understand the nature of hydrides due to their capacity for hydrogen storage,³⁵ less explored has been how different sources of hydrides can influence a particular reaction. Hence, comparative experiments using NaBH₄ as an alternative hydride source with the carbon-supported catalysts were also performed (Table 2). It is important to note that the reduction of the substrate in question by NaBH₄ has been reported to be thermodynamically feasible but kinetically restricted in the absence of a catalyst.³⁶ As expected, no reaction occurred without catalyst (entry 2) or without CaH₂ (entry 3). Under these conditions, the use of NaBH₄ was less effective than using CaH₂ in the synthesis of p-aminophenol when used in combination with Pd/C or Ru/C (entries 5 and 7) achieving only 1% and 72% yields respectively. Interestingly, the reduction of this substrate was reported by Neilson, Wood and Wylie in 1962 with 69% yield when the reaction was carried out with Pd/C at room temperature.³⁷ The use of the expensive Pt/C (entry 4) showed better results than observed with CaH₂ (Table 1, entry 1) but similar to those obtained with Ru/C and CaH₂ (entry 1), with 98% conversion and yield. These results suggested to us that CaH₂ could play an important role in the reduction. Therefore, in order to gain insights into its role in the reaction, an additional comparative experiment was performed by selecting a nitroarene containing a functionality reactive in the presence of NaBH₄. In this context, NaBH₄ is well known to afford the reduction of aromatic aldehydes to the corresponding benzyl alcohols in a reaction that proceeds without catalyst at room temperature.³⁸ Under those conditions the nitro group remains unaffected.³⁹ However, this can be transformed into the desired amine by modifying the properties of NaBH₄ in the presence of a catalyst (e.g. Pd/C). Thus, it is accepted that the surface of the catalyst is crucial for the activation of the hydrogen.⁴⁰ With this in mind, p-nitrobenzaldehyde was the substrate of choice (Table 3). From these data, we confirmed that the hydride source is a determinant for the outcome of the reaction. By using NaBH₄, a mixture of products with a different distribution ratio was observed (entries 1–4), whereas the use of CaH₂ clearly afforded more selective reactions (entries 5–8). To our delight, the chemoselective reduction of the nitro group (2ad, entry 8) was observed with Ru/C with 99% yield and conversion. On the other hand, interesting is the formation of p-methylaniline (2cd) as the main product using Pd/C or Rh/C with 92% and 70% yield respectively (entries 5 and 7). In turn, the reduction of the nitro group along with a decarbonylation reaction was observed with Pt/C with 52% yield (entry 6).

Table 2 Control experiments and NaBH₄ as hydride source^a

Entry	Catalyst	Conversion (%)	Yield (%)
a Reaction conditions: 0.5 mmol substrate, [M] (5 mol%). b CaH2 (10 mmol) in 2-MeTHF (4.0 mL) at 100 °C for 20 hours in a sealed tube. c NaBH4 (5 mmol) in 2-MeTHF (4.0 mL) at 100 °C for 20 hours in a sealed tube. Conversions, yields and ratios were determined by GC.
1^b	Ru/C	99	99
2^b	—	0	0
3^b	Ru/C	0	0
4^c	Pt/C	98	98
5^c	Pd/C	60	<1
6^c	Rh/C	99	48
7^c	Ru/C	72	72

---

Table 3 Comparative experiments using CaH₂ and NaBH₄ ^a

Entry	Cat.	Conv. (%)	Selectivity: 2ad/2bd/2cd/2dd
a Reaction conditions: 0.5 mmol substrate, [M] (5 mol%). b NaBH4 (5 mmol). c CaH2 (10 mmol), 2-MeTHF (4.0 mL), 100 °C, 20 hours. Conversions, yields and ratios were determined by GC.
1^b	Pd/C	90	1/1/4/55
2^b	Pt/C	53	3/9/11/23
3^b	Rh/C	52	2/1/25/11
4^b	Ru/C	62	1/27/13/6
5^c	Pd/C	99	0/0/92/8
6^c	Pt/C	99	0/0/48/52
7^c	Rh/C	99	0/0/70/7
8^c	Ru/C	99	99/0/0/0

---

Encouraged by these results we decided to prove the scope and generality of the methodology. Several nitroarenes containing different functionalities were screened (Table 4). The products were identified using the corresponding commercially available anilines or those prepared according to literature reports. To validate the method as a green methodology, the reaction media were filtered off, concentrated under vacuum and the ¹H NMR spectra were recorded without further purification (ESI†).

Table 4 Ru/C and CaH₂ catalyzed reduction of nitroarenes^a

Entry	Substrate	Product	Conv./sel (%)	GC yield^b (%)
a Reaction conditions: 0.5 mmol substrate, [M] (5 mol%) and CaH2 (10 mmol) in 2-MeTHF (4.0 mL) at 100 °C for 20 hours in a sealed tube. b Values in parentheses refer to isolated yields. c The reaction was scaled up 5 times.
1^c			99/99	99 (96)
2			99/99	99 (97)
3			99/99	99 (97)
4			98/99	98 (96)
5			92/99	92 (90)
6			82/99	82 (77)
7			99/99	99 (96)
8			99/99	99 (95)
9			88/93	88 (80)
10			99/99	99 (91)
11			70/99^a	70 (55)
12			73/99	73 (71)
13			97/99^b	97 (97)
14			79/99	79 (76)
15			97/99	97 (91)
16			99/99	99 (98)
17			72/99	72 (71)
18			99/99	99 (99)
19			99/99	99 (99)
20			99/99	99 (92)

---

To our delight conversions and yields up to 99%, calculated on the basis of GC analysis, were obtained. The ¹H NMR analysis of the crude products of the reactions showed the efficiency of the reduction and the catalytic system. The corresponding anilines were easily obtained in most cases without the necessity of column chromatography or other purification technique which constitutes a great advantage of the process. Remarkably, excellent selectivity was observed for all substrates containing other reducible functional groups (entries 3, 4, 9, 15 and 17). This is particularly relevant considering the selectivity problems associated with the use of heterogeneous catalysts.¹⁰ Aldehydes and ketones at 2- and 4-positions relative to the nitro group (entries 3, 4 and 9) remained unaffected during the reduction process and were obtained with good (87%) to excellent yields (99%). The corresponding ¹H NMR analysis confirmed the presence of the formyl and carbonyl groups respectively. In the case of the ester group, it was obtained with 97% yield (entry 15) and a substrate containing an ether linkage with a double bond was well tolerated (entry 17) with 72% yield. The case of halonitroarenes (entries 5, 6, 10–13) represents one of the major achievements of this methodology. These compounds have been classified as very challenging substrates because one of the major issues frequently observed with their reduction is the undesired hydrodehalogenation.¹² The C–X bond is a useful entity especially for cross-coupling reactions; therefore the presence of the halogen is relevant in molecules with nitro groups that need to be reduced. The position and nature of the halogen have also been investigated. Thus, the selectivity for the obtention of haloanilines has been ordered as F > Cl > Br > I.⁴¹ On the other hand, ortho- and para-substituted halonitroarenes have been pointed out to be more susceptible to the dehalogenation reaction than meta derivatives. From our results and in contrast to those studies, no dehalogenation was observed with 4-iodonitrobenzene, one of the most demanding and difficult substrates due to the easy hydrogenolysis of the C–I bond (entry 5, 92%). Similar result was obtained with 4-bromonitrobenzene (entry 6, 82%). ortho-Halo-substituted substrates were reduced without dehalogenation with moderate yields as in the case of 2-chloronitrobenzene (entry 11) but with good (73%) to excellent yields (99%) in the case of 2-bromo- and 2-fluoronitrobenzene respectively. Notably, in the reduction of 2-chloronitrobenzene, carried out at 10 mol% of catalyst loading, full conversion was obtained, nevertheless with a considerable amount of the dehalogenated product (41%). Therefore 5 mol% of the catalyst was used. Considering that a common strategy to suppress dehalogenation is the use of additives of different nature, metallic, acidic or basic, this methodology outperformed those methods reported in the literature since no additives are required. The selective partial reduction of 1,3-dinitrobenzene (entry 14) has already been observed with Ru/C but using molecular hydrogen at a pressure of 15 bar.⁴² The mono reduction was achieved with 79% yield along with 16% of m-phenylenediamine. Unfortunately, our attempts to obtain the latter by increasing the amount of CaH₂ failed. The method was also efficient for the reduction of polyaromatic systems, such as 1-nitronaphthalene, which was reduced with excellent yield (entry 20). Considering the safety issues related to the use of H₂, the facile procedure of this methodology constitutes another excellent alternative to the tedious and hazardous methods reported in the literature.⁴³

Because several molecules include the presence of aromatic heterocycles containing the nitro functionality, we also tested a small library of substituted nitropyridines to expand the scope of the methodology (Table 5). Moreover, the selective reduction of nitro compounds in the presence of electronically activated heteroaryl halides remains challenging since these substrates are more susceptible to hydrodehalogenation.⁴⁴

Table 5 Reduction of substituted nitropyridines^a

Entry	Substrate	Product	Conv./sel (%)	GC yield^b (%)
a Reaction conditions: 0.5 mmol substrate, [M] (5 mol%), and CaH2 (10 mmol) in 2-MeTHF (4.0 mL) at 100 °C for 20 hours in a sealed tube. b Values in parentheses refer to isolated yields.
1			99/99	97 (97)
2^a			99/99	99 (99)
3			99/99	99 (98)

---

We were pleased to observe that these substrates could also be reduced with high yields and conversions (entries 1–3). Remarkably, the reduction of 2-chloronitropyridine occurs without dehalogenation (entry 1). ¹H NMR analysis of the crude products of the reactions showed that no purification was necessary (ESI†).

Based on our experimental findings a computational study was carried out to gain more insight about the differences observed with the different catalysts addressing the question as to how metal surfaces activate the nitro group of aromatic substrates. Considering this as a binding phenomenon, the adsorption energies of the model substrate p-nitrophenol on Ru(0001), Rh(111), Pd(111), and Pt(111) surfaces were obtained with the aid of DFT calculations (see Computational Details). The corresponding adsorption energies (ΔE_bind) of the resulting binding geometries were calculated as follows:

ΔE_bind = E_adsorbate − (E_surface + E_substrate) (1)

where E_adsorbate is the energy of p-nitrophenol adsorbed on the metal surface, E_surface is the energy of clean adsorbent and E_substrate is the total energy of an isolated gas-phase p-nitrophenol molecule. From these calculations, ruthenium and rhodium surfaces exhibit the highest binding energies (−63.2 kcal mol⁻¹ and −61.8 kcal mol⁻¹, respectively) whereas platinum and palladium surfaces have binding energies of −46.4 kcal mol⁻¹ and −46.1 kcal mol⁻¹ respectively. An analysis of the resulting low-lying binding structures reveals that p-nitrophenol adopts a parallel orientation relative to the metal surface (Fig. 1 left). An alternative binding geometry involving a perpendicular orientation of the NO₂ group is less favorable than the corresponding stacked orientation by 22.4 kcal mol⁻¹ (Fig. 1 right). Careful inspection of the adsorbate geometry for the Ru(0001) surface reveals some important features of the substrate activation mode. For instance, the distance between the center of the aromatic ring and the metal surface is 2.15 Å revealing that the substate is initially physiosorbed through strong van der Waals dispersion forces. This physisorption mode also elicits a significant geometrical distortion of the nitro group with the COON improper dihedral angle deviating by 29.0° from planarity. Such geometry distortion penalty is, however, compensated by stabilizing electrostatic interactions between the oxygen atoms of the nitro group and metal atoms on the surface, with Ru–O bond lengths of 2.11 Å and 2.08 Å respectively. Interestingly, the N–O bond distances at the distorted nitro group increase regarding the isolated substrate from 1.25 Å to 1.35 Å with a concomitant decrease in N–O bond energy. At this point it must be noted that in the low-lying adsorbate geometry, the hydroxyl functionality is oriented away from the surface (Fig. 1 right) suggesting little effect on the resulting adsorption energies. We confirmed this idea, calculating the binding energies for p-nitrophenol and nitrobenzene. These values turned out to be only slightly different, with values of −63.2 kcal mol⁻¹ and −66.2 kcal mol⁻¹ respectively. Additionally and for comparative purposes, we also computed the adsorption energies for the physisorption process of benzene and phenol on the Ru(0001) surface, obtaining binding energies of −54.0 kcal mol⁻¹ and −54.3 kcal mol⁻¹ respectively, reinforcing the marginal effect of the hydroxyl group on the resulting binding energies. Thus, we propose that the geometrical deformation of the nitro group due to adsorption on the metal surface would be a key step for substrate activation and for the subsequent bond-forming and bond-cleavage steps.

Fig. 1 Computed binding geometries and adsorption energies for the physisorption of p-nitrophenol on the Ru(0001) surface.

In order to understand the factors behind the observed chemoselectivity, we also computed the adsorption energies of p-nitrobenzaldehyde on the Ru(0001) surface. As expected, for the low-lying adsorbate geometry (ΔE_bind = −78.2 kcal mol⁻¹), the substrate binds to the metal surface with the aromatic ring oriented parallel to the surface. Again, this binding mode makes both the N–O bonds longer than in the isolated substrate (1.35 Å and 1.39 Å respectively) and the improper COON dihedral angle deviating 30.0° from planarity, whereas the C=O bond is oriented nearly parallel to the surface with an improper OCHC dihedral angle of 8.5° (Fig. 2).

Fig. 2 Computed low-lying binding geometry for the physisorption of p-nitrobenzaldehyde on Ru(0001) surface.

As a result of this less geometrical deformation of the carbonyl functionality, the C–O bond elongation is less pronounced (from 1.22 Å to 1.30 Å) than that observed with the nitro group, highlighting that the adsorbed nitro functionality is more activated for the bond-forming and bond-cleavage processes and in consequence selectively reduced. However, elucidating the detailed mechanism of this transformation, including the role of the hydride source in the reaction, requires further theoretical and experimental studies beyond of the scope of the present work.

Experimental

General procedure

The corresponding nitro (hetero)arene (0.5 mmol) and Ru/C (5%; 5–10 mol%) were weighed into a 15 mL sealed tube and 4 mL of 2-MeTHF was added to the tube followed by CaH₂ (10 equiv.). The reaction mixture was allowed to stir at 100 °C for 20 h. After cooling, the reaction was then filtered through a millipore syringe filter (Durapore (PVDF) with graduated multilayer glass prefilter, 25 mm diameter, 0.45 μm). 0.5 μL of the filtrated reaction was added to a vial containing additional 0.5 μL of 2-MeTHF and injected into a GC. The remaining solution was concentrated under vacuum and the corresponding ¹H NMR spectra were recorded.

Computational details

All calculations were performed with CP2K 7.1⁴⁵ using periodic boundary conditions. The wavefunctions and the electronic density were represented and extrapolated by the hybrid Gaussian and plane wave (GPW) method within the QuickStep module.⁴⁶ Energy and force evaluations were performed using the PBE exchange–correlation functional (PBE96),⁴⁷ with the Becke–Johnson damped Grimme's correction scheme DFT-D3(BJ) to account for dispersion interactions,⁴⁸ with a cutoff radius of 32.0 Å and three-body terms. The molecular orbital occupation numbers were smeared with the Fermi–Dirac distribution at an electronic temperature of 300 K. The valence electron (Kohn–Sham) wavefunctions of all elements were expanded using the DZVP-MOLOPT gaussian basis set (-SR version for metallic elements),⁴⁹ with the corresponding pseudopotential from the GTH library.⁵⁰ Explicit valence shells included are: H(1s), C(2s2p), N(2s2p), O(2s2p), Br(4s4p), Ru(4s4p4d5s), which correspond to 1, 4, 5, 6, 7 and 16 valence electrons, respectively. The density was represented with a plane wave energy cutoff of 750 Ry, and a multigrid of five levels with a relative cutoff of 60 Ry. We used a convergence criterion of 10⁻⁷ for SCF cycles. Metallic ruthenium was optimized by means of simultaneous relaxation of cell and geometry over a two-atom hexagonal primitive cell [MP-Ru], maintaining cell symmetry and angles, at 0,1 kbar and using a Γ-centered Monkhorst–Pack k-point grid of 11 × 11 × 6. The ruthenium slab model was constructed for the (0001) surface with eight-atom layer thickness by means of geometrical relaxation with a Γ-centered Monkhorst–Pack k-point grid of 11 × 11 × 1. Finally, adsorption of organic molecules (through different functional groups of the molecules) on ruthenium was carried out with a 6 × 6 expanded Ru(0001) surface with a single Γ-centered k-point, constraining the position of the last three atomic layers of ruthenium.

Conclusions

We have developed a new and simple synthetic methodology for the reduction of aromatic and heteroaromatic nitro compounds using Ru/C and CaH₂ as hydride source. Our findings showed the key role of CaH₂ which acts in a synergistic manner with the heterogeneous catalyst allowing one to reach high conversions and selectivities of nitro compounds containing other reducible functionalities. In addition, halonitroarenes can also be reduced without dehalogenation. In this context the reported method overcomes one of the main problems associated with the use of heterogeneous catalysts. The reaction proceeds without the use of additives in 2-MeTHF as an environmentally friendly solvent. In addition, the corresponding anilines can be obtained by simple filtration without the necessity of further purification. Because of this operational simplicity, the process aims to be an alternative to other reported methods.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

Powered@NLHPC: This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM-02). S. G.-F. acknowledges financial support by the ANID project FONDECYT Iniciación No. 11221216. We acknowledge the FONDECYT Regular Project No. 1210708.

References

1. H. K. Porter, in Organic Reactions, John Wiley & Sons, Hoboken,NJ, 2011, p. 455.
2. N. Ono, The Nitro Group in Organic Synthesis, John Wiley & Sons, New York, NY, 2001.
3. (a) F. Ullmann, W. Gerhartz, Y. S. Yamamoto, F. T. Campbell, R. Pfefferkorn and J. F. Rounsaville, Ullmann's Encyclopedia of Industrial Chemistry, Verlag Chemie, Weinheim, Germany, 2012, vol. A2, pp. 647–718; (b) P. N. Rylander, Catalytic Hydrogenation in Organic Syntheses, Academic Press, 1979; (c) S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis, John Wiley & Sons, 2001; (d) R. M. Bullock, Science, 2013, 342, 1054–1055; (e) A. M. Smith and R. Whyman, Chem. Rev., 2014, 114, 5477–5510.
4. W. G. Jia, M. X. Cheng, Q. T. Xu, L. L. Gao and G. Yuan, Polyhedron, 2018, 69–75.
5. M. Orlandi, D. Brenna, R. Harms, S. Jost and M. Benaglia, Org. Process Res. Dev., 2018, 22, 430–445.
6. (a) A. M. Tafesh and J. Weiguny, Chem. Rev., 1996, 96, 2035–2052; (b) S. Cenini and F. Ragaini, Catalytic Reductive Carbonylation of Organic Nitro Compounds, Kluwer Academic Press, Dordrecht, 1996; (c) L. He, L. C. Wang and H. Sun, Angew. Chem., Int. Ed., 2009, 48, 9538–9541; (d) J. Huang, L. Yu and L. He, Green Chem., 2011, 13, 2672–2677; (e) K. Nomura, J. Mol. Catal. A: Chem., 1995, 95, 203; (f) F. Ragaini and S. Cenini, J. Mol. Catal. A: Chem., 1996, 105, 145; (g) L. Liu, B. Qiao, Z. Chen, J. Zhang and Y. Deng, Chem. Commun., 2009, 653; (h) F. A. Westerhaus, I. Sorribes, G. Wienhöfer, K. Junge and M. Beller, Synlett, 2015, 26, 313.
7. (a) L. Gregor, A. K. Reilly, T. A. Dickstein, S. Mazhar, S. Bram, D. G. Morgan, Y. Losovyj, M. Pink, B. D. Stein, V. G. Matveeva and L. M. Bronstein, ACS Omega, 2018, 3, 14717–14725; (b) Y. Duan, X. Dong, T. Song, Z. Wang, J. Xiao, Y. Yuan and Y. Yang, ChemSusChem, 2019, 12, 4636.
8. D. Formenti, F. Ferretti, F. K. Scharnagl and M. Beller, Chem. Rev., 2019, 119, 2611–2680.
9. (a) X. Chen, X. Y. Zhou, H. Wu, Y. Z. Lei and J. H. Li, Synth. Commun., 2018, 48, 2475–2484; (b) Q. Tang, Z. Yuan, S. Jin, K. Yao, H. Yang, Q. Chi and B. Liu, React. Chem. Eng., 2020, 5, 58; (c) B. Zeynizadeh, F. Mohammad Aminzadeh and H. Mousavi, Res. Chem. Intermed., 2021, 47, 3289–3312.
10. (a) H. S. Wei, X. Y. Liu, A. Q. Wang, L. L. Zhang, B. T. Qiao, X. F. Yang, Y. Q. Huang, S. Miao, J. Y. Liu and T. Zhang, Nat. Commun., 2014, 5, 8; (b) Y. J. Shu, H. C. Chan, L. F. Xie, Z. P. Shi, Y. Tang and Q. S. Gao, ChemCatChem, 2017, 9, 4199–4205; (c) H. U. Blaser, H. Steiner and M. Studer, ChemCatChem, 2009, 1, 210–221.
11. (a) Z. N. Hu, J. Liang, K. Ding, Y. Ai, Q. Liang and H. B. Sun, Appl. Catal., A, 2021, 626, 118339; (b) S. Sun, M. Du, R. Zhao, X. Jv, P. Hu, Q. Zhang and B. Wang, Green Chem., 2020, 22, 4640–4644.
12. M. Pietrowski, Curr. Org. Chem., 2012, 9, 470–487.
13. R. F. Nystrom and W. G. Brown, J. Am. Chem. Soc., 1948, 70(11), 3738–3740.
14. (a) P. Carson and C. Mumford, Hazardous Chemicals Handbook, Butterworth-Heinemann, Oxford, 2nd edn, 2002, p. 232; (b) G. Weiss, Hazardous Chemicals Data Book, Noyes Data Corporation, New York, 2nd edn, 1985, p. 639.
15. E. R. Burkhardt and K. Matos, Chem. Rev., 2006, 106, 2617.
16. B. M. Trost and I. Fleming, Comprehensive Organic Synthesis, Selectivity, Strategy and Efficiency in Modern Organic Chemistry, Pergamon, Oxford, 1991.
17. (a) B. Zeynizadeh and K. J. Zahmatkesh, Chin. Chem. Soc., 2003, 50, 267; (b) M. Periasamy and M. J. Thirumalaikumar, Organomet. Chem., 2000, 609, 137; (c) A. Rahman and S. B. Jonnalagadda, Catal. Lett., 2008, 123, 264; (d) I. Pogorelić, M. Filipan-Litvić, S. Merkaš, G. Ljubić, I. Cepanec and M. J. Litvić, Mol. Catal. A: Chem., 2007, 274, 202; (e) T. Satoh, S. Suzuki, Y. Suzuki, Y. Miyaji and Z. Imai, Tetrahedron Lett., 1969, 10, 4555.
18. R. E. Gawley and A. Davis, Calcium Hydride, Encyclopedia of Reagents for Organic Synthesis, 2001,  DOI:10.1002/047084289X.rc005.
19. K. Nagashima, H. Visbal and K. Hirao, Int. J. Appl. Ceram. Technol., 2016, 13, 265–268.
20. T. Aida, N. Kuboki, K. Kato, W. Uchikawa, C. Matsuno and S. Okamoto, Tetrahedron Lett., 2005, 46, 1667–1669.
21. A. Tsuhako, J. Q. He, M. Mihara, N. Saino and S. Okamoto, Tetrahedron Lett., 2007, 48, 9120–9123.
22. (a) C. Guyon, E. Da Silva, R. Lafon, E. Métay and M. Lemaire, RSC Adv., 2015, 5, 2292; (b) C. Guyon, M.-C. Duclos, M. Sutter, E. Métay and M. Lemaire, Org. Biomol. Chem., 2015, 13, 7067–7075.
23. (a) M. Vilches-Herrera, S. Gallardo-Fuentes, M. Aravena-Opitz, M. Yáñez-Sánchez, H. Jiao, J. Holz, A. Börner and S. Lühr, J. Org. Chem., 2020, 85, 9213–9218; (b) M. Vilches-Herrera, S. Werkmeister, K. Junge, A. Börner and M. Beller, Catal. Sci. Technol., 2014, 4, 629–632.
24. (a) M. Misra, S. R. Chowdhury and T. I. Lee, Appl. Catal., B, 2020, 272, 118991; (b) Z. Wu, X. Yuan and H. Zhong, et al. , Sci. Rep., 2016, 6, 25638.
25. Z. Dong, X. Le, X. Li, W. Zhang, C. Dong and J. Ma, Appl. Catal., B, 2014, 129–135.
26. (a) X. Zhu, S. Liang, S. Chen, X. Liu and R. Li, Catal. Sci. Technol., 2020, 10, 8332–8338; (b) P. P. Ghimire, L. Zhang and U. A. Kinga, et al. , J. Mater. Chem. A, 2019, 7, 9618–9628; (c) I. Ibrahim, I. O. Ali and T. M. Salama, et al. , Appl. Catal., B, 2016, 181, 389–402.
27. S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation for Organic Synthesis, Wiley-Interscience, 2001.
28. X. Wang, M. Liang, J. Zhang and Y. Wang, Curr. Org. Chem., 2007, 11, 299–314.
29. (a) N. Lezana, A. Galdámez, S. Lühr and M. Vilches-Herrera, Green Chem., 2016, 18, 3712–3717; (b) M. Concha, A. Cortínez, N. Lezana, M. Vilches-Herrera and S. Lühr, Catal. Sci. Technol., 2022, 12, 6833–6890.
30. V. Pace, P. Hoyos, L. Castoldi, P. Dominguez de María and A. R. Alcántara, ChemSusChem, 2012, 5, 1369–1379.
31. P. Anastas and N. Eghbali, Chem. Soc. Rev., 2010, 39, 301–312.
32. D. J. C. Constable, A. D. Curzons and V. L. Cunningham, Green Chem., 2002, 4, 521–527.
33. P. G. Jessop, Green Chem., 2011, 13, 1391–1398.
34. R. Palkovitz, Angew. Chem., Int. Ed., 2010, 49, 4336–4338.
35. Q. Wang, J. Guo and P. Chen, Joule, 2020, 4, 705–709.
36. B. Baruah, G. J. Gabriel, M. J. Akbashev and M. E. Booher, Langmuir, 2013, 29, 4225–4234.
37. T. Neilson, H. C. S. Wood and A. G. Wylie, J. Chem. Soc., 1962, 371–372.
38. (a) A. Wolfson and C. Dlugy, Org. Commun., 2009, 2, 34–41; (b) S. Y. Han, E. M. Shulman-Roskes, K. Misiura, L. W. Anderson, E. Szymajda, M. P. Gamcsik, Y. H. Chang and S. M. Ludeman, 34, 1994, 247–254.
39. (a) S. Senaweera and J. D. Weaver, Chem. Commun., 2017, 53, 7545–7548; (b) J. Desroches, P. A. Champagne, Y. Benhassine and J.-F. Paquin, Org. Biomol. Chem., 2015, 13, 2243–2246.
40. W. B. Smith, J. Heterocycl. Chem., 1987, 24, 745–748.
41. (a) M. Pietrowski, Selective hydrogenation of unsaturated functional groups over heterogeneous ruthenium catalysts, in Ruthenium: Properties, Production and Applications, ed. D. B. Watson, Nova Science Pub Inc., 2011; (b) R. L. Augustine, Heterogeneous Catalysis for the Synthetic Chemist, CRC Press, 1996, p. 672; (c) J. R. Kosak, Catalysis in organic synthesis, Academic Press, 1980; (d) H. U. Blaser, A. Schnyder, H. Steiner, F. Rössler and P. Baumeister, Selective Hydrogenation of Functionalized Hydrocarbons, in Handbook of Heterogeneous Catalysis, ed. G. Ertl, H. Knözinger, F. Schüth and J. Weitkamp, Wiley-VCH, 2008, vol. 8.
42. J. Hou, Y. Ma, Y. Li, F. Guo and L. Lu, Chem. Lett., 2008, 37, 974–975.
43. (a) T. W. Graham Solomons and C. B. Fryhle, Organic Chemistry, John Wiley & Sons, New York, 7th edn, 2000, p. 701; (b) W. Herbst and K. Hunger, Industrial Organic Pigments: Production, Properties, Applications, Wiley-VCH, Weinheim, 3rd rev. edn, 2004, p. 185; (c) S. A. Lawrence, Amines: Synthesis, Properties and Applications, Cambridge University Press, Cambridge, 2004, p. 77.
44. A. Kasparian, C. Savarin, A. Allgeier and Sh. Walker, J. Org. Chem., 2011, 76, 9841–9844.
45. (a) J. Hutter, M. Iannuzzi, F. Schiffmann and J. VandeVondele, Wiley Interdiscip. Rev.: Comput. Mol. Sci., 2014, 4, 15–25; (b) T. D. Kühne, M. Iannuzzi, M. Del Ben, V. V. Rybkin, P. Seewald, F. Stein, T. Laino, R. Z. Khaliullin, O. Schütt, F. Schiffmann, D. Golze, J. Wilhelm, S. Chulkov, M. Hossein, M. H. Bani-Hashemian, V. Weber, U. Borštnik, M. Taillefumier, A. Shoshana Jakobovits, A. Lazzaro, H. Pabst, T. Müller, R. Schade, M. Guidon, S. Andermatt, N. Holmberg, G. K. Schenter, A. Hehn, A. Bussy, F. Belleflamme, G. Tabacchi, A. Glöβ, M. Lass, I. Bethune, C. J. Mundy, C. Plessl, M. Watkins, J. VandeVondele, M. Krack and J. Hutter, J. Chem. Phys., 2020, 152, 194103.
46. J. VandeVondele, M. Krack, F. Mohamed, M. Parrinello, T. Chassaing and J. Hutter, Comput. Phys. Commun., 2005, 167, 103–128.
47. J. P. Perdew, K. Burke and M. Ernzerhof, Phys. Rev. Lett., 1997, 78, 1396.
48. S. Grimme, S. Ehrlich and L. Goerigk, J. Comput. Chem., 2011, 32, 1456–1465.
49. J. VandeVondele and J. Hutter, J. Chem. Phys., 2007, 127, 114105.
50. (a) S. Goedecker, M. Teter and J. Hutter, Phys. Rev. B: Condens. Matter Mater. Phys., 1996, 54, 1703; (b) C. Hartwigsen, S. Goedecker and J. Hutter, Phys. Rev. B, 1998, 58, 3641.

---

Footnote

† Electronic supplementary information (ESI) available. See DOI: https://doi.org/10.1039/d2ob01807a

---