https://doi.org/10.3311/PPch.12787 476|Creative Commons Attribution b Periodica Polytechnica Chemical Engineering, 62(4), pp. 476–488, 2018 Selective Heterogeneous Catalytic Hydrogenation of Nitriles to Primary Amines Krisztina Lévay1, László Hegedűs1* 1 Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O.B. 91, Hungary * Corresponding author, e-mail: [email protected] Received: 02 July 2018, Accepted: 30 August 2018, Published online: 01 October 2018 Abstract Primary amines are important intermediates, especially in the area of pharmaceutical, plastic and agrochemical industry. The heterogeneous catalytic hydrogenation of nitriles is one of the most frequently applied process for the synthesis of diverse amines. However, the control of the selectivity is a critical issue in this reaction. Over the past decade, many studies have been reported using heterogeneous transition metal catalysts for the selective reduction of nitriles to the corresponding primary amines. The type of the catalysts, especially, the chemical nature of metals in the catalysts is one of the most important factors to influence the selectivity, the reaction rate, and possibly also the reaction pathway and the deactivation of the catalyst. Thus, this review focuses on the heterogeneous transition metal catalysts and summarizes the recent developments achieved in the selective catalytic hydrogenation of nitriles to primary amines. Keywords heterogenous catalysis, hydrogenation, nitriles, primary amines, selective reduction 1 Introduction Primary amines are one of the most important intermedi- of the selectivity. Depending on the structure of the sub- ates, especially in the area of pharmaceutical, plastic and strate, the nature and amount of the catalyst and the reac- agrochemical industry. There are several methodologies tion conditions, one of the amine types mentioned above for the synthesis of primary amines, including the reduc- can predominate in the hydrogenation products. tion of nitro compounds, amides and the reductive amina- Among these factors, the chemical nature of the cat- tion of oxo compounds [1, 2]. alytic metal has a decisive influence on the composition The heterogeneous catalytic hydrogenation of nitriles of the products [8, 9]. Nevertheless, there are some pos- is the most preferred synthetic method in the industrial sibilities to enhance the selectivity to primary amine. production of primary amines. Although the conversion With addition of ammonia [7, 10–15] or an appropriate of the nitrile group to a primary amine one takes place base [7, 16–18] the formation of by-products could be sup- relatively easily, but the selectivity of the reaction can pressed. Using ammonia, however, high primary amine be strongly decreased due to the formation of by-prod- selectivities were only reported with Raney® nickel [10– ucts [3–5]. The reaction mechanism of hydrogenation of 14] or rhodium [15] catalysts, while over supported pal- nitriles was proposed for the first time by von Braun et ladium or platinum catalysts, the main product remained al. [6] and later modified by Greenfield [7]. Due to the the secondary / tertiary amine even in the presence of five high reactivity of the imine intermediate 2, the hydroge- equivalents of NH3 [7, 13]. Furthermore, the positive effect nation of nitriles 1 leads to a set of consecutive and par- of the bases (e.g. aqueous solutions of NaOH, LiOH, KOH allel reactions and results in a mixture of primary 3, sec- or Na2CO3) on the product distribution was also revealed ondary 4 and tertiary amines 5, as shown in Fig. 1. The for only cobalt and nickel catalysts [7, 16–18]. separation of the reaction products is usually complicated Avoiding the reaction between the primary amine (3) due to the small differences in their boiling points. For and the imine intermediate (2) also represents a possibil- this reason, one of the most critical issues is the control ity to effectively minimize the formation of secondary (4) Cite this article as: Lévay, K., Hegedűs, L. "Selective Heterogeneous Catalytic Hydrogenation of Nitriles to Primary Amines", Periodica Polytechnica Chemical Engineering, 62(4), pp. 476–488, 2018. https://doi.org/10.3311/PPch.12787 Lévay and Hegedűs Period. Polytech. Chem. Eng., 62(4), pp. 476–488, 2018| 477 Figure 1 2 Base metal catalysts 2.1 Nickel-catalyzed hydrogenations Nickel is a typically applied catalyst in the hydrogena- tion of nitriles in different forms, such as Raney-type one [10–14, 16–18, 24, 25], supported on silica [7, 26–30], alu- Figure 1mina [31–34] or sepiolite [35], as well as NiAl alloy [36], Ni nanoparticles [37–39] or Ni2P [40]. In 2009, Hoffer and Moulijn [25] investigated the hydro- genation of aliphatic dinitriles (succinonitrile 6a, glutaroni- trile 6b and adiponitrile 6c) to the corresponding aminoni- triles (7a-c) at 77 °C and 50 bar over commercial Raney®-Ni catalyst (Fig. 2). Based on their results, the reactivity of the substrates and the mechanism of the hydrogenation were highly influenced by the hydrocarbon chain length. Short dinitriles, like compound 6a, exhibit stronger adsorption on the catalyst surface than longer dinitriles, such as compound Fig. 1 Reaction pathways in the hydrogenation of nitriles 6c. Furthermore, with increasing of the hydrocarbon chain length, a substantial decrease was achieved in the yields of and/or tertiary amines (Figure5). This 2 can be obtained by form- the partial hydrogenated intermediates (7a-c), due to the ing a salt with acids [19–21] or by acylating the amino enhanced competitiveness of dinitriles (6a-c) and amino- group with acetic anhydride [22–24]. nitriles (7a-c) for the same active sites. Moreover, a longer Taking into account all of these considerations, this chain length had a negative effect on the reactivity of the review summarizes the recent developments achieved in first C≡N bond, because the destabilizing effect of the elec- the selective heterogeneous catalytic hydrogenation of tron-withdrawing second C≡N bond was weakened. Thus, it nitriles to primary amines. The information gathered is was found that both the reaction rate and the adsorption Figure 2 discussed on the basis of the chemical nature of the cata- strength decrease in the following order: succinonitrile (6a) lytic metals used in this hydrogenation. > glutaronitrile (6b) > adiponitrile (6c) (Table 1). Figure 3 Fig. 2 Mechanism of the catalytic hydrogenation of dinitriles, such as succinonitrile (6a), glutaronitrile (6b) and adiponitrile (6c) Figure 3 Lévay and Hegedűs 478|Period. Polytech. Chem. Eng., 62(4), pp. 476–488, 2018 ® Table 1 Hydrogenation of dinitriles over Raney -Ni catalyst NH2 CN Selectivity to the Activity H2, KNiCo/Al2O3 Entry Substrate –1 –1 corresponding (mol kgcat min ) aminonitrile (7a-c) toluene/MeOH=4:1 NH2 CN NaOH 1 6a 0.78 95 80 °C, 60 bar 2 6b 0.44 90 13 14 3 6c 0.28 70 Fig. 3 Hydrogenation of isophthalonitrile (11) to m-xylylenediamine Conditions: 77 °C, 50 bar, ethylenediamine (solvent) (12) over a K-doped NiCo/Al2O3 catalyst In 2012, Apesteguía et al. [27] studied the liquid-phase alcohol ones that inhibit butylamine adsorption on the cat- hydrogenation of butyronitrile to butylamine over silica alyst and thereby, decrease the formation of by-products. supported transition metal (Ni, Co, Ru, Cu, Pd, Pt) cat- In 2016, Han et al. [29] also investigated the hydroge- alysts at 100 °C and 13 bar, in ethanol. The butylamine nation of adiponitrile (6c) to 6-aminocapronitrile (7c) and selectivity was in the following order: Ni > Co > Ru > Pt. 1,6-hexamethylenediamine (9c), which are very important However, the formation of the desired product was not monomers in some industrial processes for manufacturing observed over Cu/SiO2 and Pd/SiO2 catalysts due to the synthetic fibers (nylon-6 and nylon-6,6), but his time over a fast deactivation. Furthermore, Pt/SiO2 produced mainly Ni/SiO2 catalyst prepared by direct reduction of Ni(NO3)2/ dibutylamine and only minor amounts of butylamine and SiO2. According to the previously described mechanism tributylamine. In an attempt to reduce the formation of (Fig. 2), this catalyst system effectively inhibited the conden- by-products, Ni/SiO2, Co/SiO2, Ru/SiO2 (the latter two sation reactions by promoting the hydrogenation of adsorbed will be discussed in Sections 2.2 and 3.2) catalysts were imine (8c). Good selectivity to primary amines (79% for 7c tested to optimize the reaction conditions (solvents, tem- and 9c) was achieved, after 86% conversion of 6c, in metha- perature, pressure). The highest selectivity to butylamine nol, in the presence of NaOH, at 80 °C and 30 bar. (84%) was achieved in ethanol (Table 2, entry 1), while In 2014, Liu and Wang [31] reported the selective hydro- using benzene, toluene or cyclohexane the primary amine genation of isophthalonitrile (11) to m-xylylenediamine selectivity significantly decreased to 63–39% (Table 2, (12) over Ni–Co on alumina catalysts modified by potas- entries 2–4) [28]. These results suggest that using a protic sium (Fig. 3). The reactions were carried out at 80 °C and solvent influences the strength of the solvent–butylamine 60 bar, in the presence of basic additives. It was observed interaction in the liquid phase, which positively affects that the K-modification considerably decreased the cata- the selectivity of primary amine over Ni/SiO2. Ethanol, lyst acidity. Besides, when KNiCo/Al2O3 (K: 3 wt%) was as a H-bond donor