An efficient copper catalyzed formylation of amines utilizing CO₂ and hydrogen

Abstract

Trans-Bis-(glycinato)copper(II) complex was found to be a highly active, economical and efficient heterogeneous catalyst for the formylation of amines utilizing CO₂ and hydrogen under solvent free conditions.

---

Chemical fixation of carbon dioxide (CO₂) to high value chemicals has gained considerable interest in recent years due to the gowning environmental concerns and its abundant availability at low cost. Replacement of toxic and hazardous C1 building blocks such as phosgene, carbon monoxide with non-toxic CO₂ represents a green and sustainable approach for the synthesis of carbonyl group derived industrially important chemicals such as urea, alkyl carbonates, formamides, carbamates and isocynates.¹ The formylation of amines using CO₂ and hydrogen is of great importance due to versatile applications of formamides such as solvent, in the manufacture of polyurethane leatherette, polyacronitrile fiber and pharmaceutical industry.² In this context a number of transition metal based catalysts such as iridium oxide cluster dispersed in titania, silica hybrid aerogels containing bidentate ruthenium complexes, Pd(CO₃)[P(C₆H₅)₃]₂, RuCl₂[P(CH₃)₃]₄ etc. have been reported.³ However, in most of the cases the use of expensive metal catalysts, rapid deactivation of the catalyst and severe reaction conditions make the developed processes less attractive for large scale synthesis. Recently, Feng Shi et al. have demonstrated the use of Pd/Al₂O₃-NRs as efficient heterogeneous catalyst for amine formylation.⁴ However, the use of expensive Pd metal, two step process of catalyst synthesis and longer reaction time still leaves a scope for the further development of an efficient and cost effective methodology for this transformation.

In the present we disclose for the first time an efficient, easily accessible and inexpensive bis-(glycinato)copper(II) i.e. Cu(gly)₂ complex as a recyclable catalyst for the formylation of various secondary amines including aliphatic and aromatic using CO₂ and H₂ under solvent less conditions (Scheme 1).

Scheme 1 Cu(gly)₂ catalysed formylation of amines.

The Cu(gly)₂ complex was easily obtained from the reaction of copper chloride and glycine in ethanol under refluxing condition in almost quantitative yields. The synthesized catalyst was characterized by XRD, XPS, FT-IR, and TGA. Detailed synthetic procedure and characterization of the catalyst is given in ESI file.† The chemical nature and functionalities presented in Cu(gly)₂ complex were revealed by FT-IR (Fig. S1†). Two intense peaks at 1604 and 1389 cm⁻¹ in the spectrum of Cu(gly)₂ are attributed to COO⁻ asymmetric and symmetric stretches, respectively. Furthermore, strong bands at 3334 and 1423 cm⁻¹ are due to N–H stretch and bending vibrations of amino functional groups of glycine revealed the formation of Cu(gly)₂ complex.⁵ Importantly, O–H stretching vibration do not appear in complex in the range (3450–3750) cm⁻¹ suggesting the absence of the lattice and coordinated water. XPS analysis of Cu(gly)₂ complex was carried out to elucidate the chemical interaction between the CuCl₂ and glycine (Fig. 1). The survey scan XPS spectra explicitly demonstrated the presence of C, N, O, and Cu elements. The high-resolution Cu 2p spectrum exhibited split bands of Cu 2p peak at 936.1 and 956.8 eV due to Cu 2p_3/2 and Cu 2p_1/2, respectively is consistent with Cu(II) oxidation state.⁶ XRD pattern of the Cu(gly)₂ complex (Fig. 1c), exhibits strong peaks and are found to be identical to the pure Cu(gly)₂ (JCPDS card no. 17-1814).⁷ TG analysis results of Cu(gly)₂ complex is depicted in (Fig. 1d). The TG curve recorded under N₂ atmosphere at 10 °C min⁻¹ heating rate shows a single step weight loss at temperatures ranging from 50 °C to 600 °C. It is observed that there is no weight loss until 250 °C, which further confirms the absence of lattice water molecules. TGA results are in good agreement with the results of FT-IR. The values of elemental analyses (found: C, 22.41%; H, 3.52%, N, 13.33%; cal: C, 22.70%, H, 3.81%, N, 13.23%) suggested the proposed formula of complex is Cu(gly)₂. These results suggested the successful formation of the substantive Cu(gly)₂ complex.

Fig. 1 (a) Broad scan XPS spectra of Cu(gly)₂; (b) high resolution XPS spectra of Cu 2p; (c) XRD of Cu(gly)₂; and (d) TGA of Cu(gly)₂.

The catalytic activity of the synthesized heterogeneous catalyst i.e. Cu(gly)₂ was tested for the formylation of various primary and secondary amines including aliphatic and aromatic to the corresponding formamides by using CO₂ and hydrogen. At first, diethyl amine was chosen as a model substrate to optimize the reaction conditions. The experiments were carried out in a stainless steel 15 ml autoclave under stirring at 85 °C and 50 bar pressure for 4 h. The maximum formylation of diethyl amine under the optimized reaction condition was found to be 95% as shown in Table 1, entry 4.

Table 1 Catalytic activity of Cu(gly)₂ over its analogue^a

Entry	Catalyst (mol%)	Yield (%)	Selectivity (%)
a Reaction conditions: diethyl amine (5 ml); catalyst (0.1 g); molar ratio of CO2/H2 (1.25); total pressure of reaction (50 bar); reaction time 4 h.
1.	—	—	—
2.	CuCl2	21	75
3.	CuCl2/Glycine	39	71
4.	Trans-Cu-(Gly)2	95	98
5.	Cis-Cu(Gly)2·H2O	71	95
6.	Trans-Cu(Gly)2·H2O	70	92

---

In the absence of any catalyst, no reaction was taken place under identical experimental conditions (Table 1, entry 1). In order to compare the catalytic activity of the developed heterogeneous catalyst with its homogeneous analogue, we also carried out the formylation of diethyl amine from hydrogen and CO₂ using homogeneous copper CuCl₂ and mix of CuCl₂/glycine as catalyst under described experimental conditions. The results are summarized in Table 1 (entry 2 and 3).

In the present study, we observed that trans-Cu(gly)₂ complex exhibited higher catalytic activity as compared to its hydrated cis-and trans-analogues (Table 1, entry 4–6). The lower catalytic activity of the hydrated complexes might be due to the presence of water molecules on the axial position⁸ which hindered the copper to interact with hydrogen from one side. While in case of trans-Cu(gly)₂ both the axial positions are free to interact with hydrogen and therefore gave higher rate of the reaction. Besides these experiments, we also investigated the effect of temperature, molar ratio of CO₂ and H₂, and reaction time on the formylation of diethyl amine under described reaction conditions. At ambient temperature (25 °C), the reaction rate was found to be slow and depended on the CO₂ pressure applied (Fig. 2a). Among the various conditions 85 °C temperature and 50 bar CO₂ pressure was found to be optimum for maximum conversion of diethyl amine to corresponding formamide. Further increase in temperature (120 °C) was found to be unsuitable and exhibited significant decrease in the formylation of diethyl amine. This may be due to the formation of undesired N-methylated by-products. In addition, the reaction was found to be increased with increasing the molar ratio of CO₂ and H₂ up to 1.25 (Fig. 2b). Further increase in CO₂/H₂ molar ratio did not affect the reaction to any significant extent (Fig. 2b). Next, we studied the effect of the reaction time on the yield of the formylated product (Fig. 2c). The yield of the desired product was found to be increased with time up to 4 h, however further increase in reaction time did not influence the reaction to any considerable level.

Fig. 2 (a) Effect of temperature on the yield of product at 50 bar; (b) effect of molar ratio of CO₂/H₂ on the yield of product keeping reaction pressure 50 bar at 85 °C; (c) effect of time on the yield of product at 85 °C and 50 bar CO₂ pressure; and (d) recyclability of the catalyst.

Furthermore, we checked the recycling ability of the recovered catalyst. The results of the recycling experiments are summarized in Fig. 2d. The recovered catalyst exhibited almost similar activity under identical conditions at least for five runs. Moreover, to ascertain the leaching of metal, we analyzed the reaction mixture after separating catalyst by ICP-AES analysis. No detectable leaching of copper could be observed during the course of reaction which further proved that the developed catalyst is truly heterogeneous in nature.

Furthermore, the reaction was extended to a variety of secondary amines including aliphatic and aromatic under the optimized reaction conditions. The results of these experiments are summarized in Table 2. The reaction proceeded successfully and afforded 81–95% yield of the desired product in all cases (Table 2, entry 1, 2, 4–8) except in N-methyl aniline (Table 1, entry 3). The lower reactivity of N-methyl aniline might be due to the presence of aromatic ring and steric hindrance.

Table 2 Cu(Gly)₂ catalyzed formylation of amines^a

Entry	Substrate	Product	Yield (%)	Select. (%)
a Reaction conditions: amine (5 ml); catalyst (0.1 g); molar ratio of CO2/H2 = 1.25; total pressure of reaction 50 bar; 85 °C; 4 h.
1.			91	96
2.			95	98
3.			41	85
4.			95	97
5.			91	97
6.			90	96
7.			81	91
8.			92	95

---

Although, the exact mechanism of the reaction is not clear at this stage, based on the existing literature reports,⁹ a plausible mechanism for the reaction is shown in Scheme 2. In analogy to the previous reports, we presumed that Cu activates the H₂ which reacts with CO₂ to give HCOOH. Formic acid subsequently reacts with amine in the dehydration step to give corresponding formamides. It is also clear from the mechanism that high pressure of CO₂ is favourable to shift the equilibrium towards forward direction.

Scheme 2 Possible reaction mechanism.

In summary, we have developed an easily accessible, cost effective copper(II) glycinato to be used as highly efficient, recyclable and selective catalyst for the formylation of secondary amines directly from the reaction of CO₂ and H₂ without using any solvent.

Notes and references

1. (a) A. H. Liu, Y. N. Li and L. N. He, Pure Appl. Chem., 2012, 84, 411–860; (b) M. Aresta, Carbon dioxide as chemical feedstock, John Wiley & Sons, 2010; (c) T. Sakakura, J. C. Choi and H. Yasuda, Chem. Rev., 2007, 107, 2365; (d) L. N. He, Z. Z. Yang, A. H. Liu, J. Gao and Y. H. Hu, Advances in CO₂ Conversion and Utilization, ACS, Washington, DC, 2010, ACS Symposium Series No. 1056, pp. 77–101; (e) J. L. Wang, C. X. Miao, X. Y. Dou, J. Gao and L. N. He, Curr. Org. Chem., 2011, 15, 621.
2. (a) K. Weissermel and H. J. Arpe, Industrial Organic Chemistry, Wiley-VCH, Weinheim, 2003, p. 43; (b) S. Ding and N. Jiao, Angew. Chem., Int. Ed., 2012, 51, 9226–9237.
3. (a) Q. Y. Bi, J. D. Lin, Y. M. Liu, S. H. Xie, H. Y. He and Y. Cao, Chem. Commun., 2014, 50, 9138–9140; (b) P. G. Jessop, Y. Hsiao, T. Ikariya and R. Noyori, J. Am. Chem. Soc., 1994, 116, 8851–8852; (c) L. Schmid, M. Rohr and A. Baiker, Chem. Commun., 1999, 2303–2304; (d) P. Haynes, L. H. Slaugh and J. F. Kohnle, Tetrahedron Lett., 1970, 11, 365–368.
4. (a) X. Cui, Y. Zhang, Y. Deng and F. Shi, Chem. Commun., 2014, 50, 189–191.
5. (a) F. H. A. Al-Jeboori and T. A. M. Al-Shimiesawi, J. Chem. Pharm. Res., 2013, 5(11), 318–321.
6. (a) C. Huo, J. Ouyang and H. Yang, Sci. Rep., 2014, 4.
7. (a) W. Li, L. Lang, J. Dianzeng, C. Yali and X. Xinquan, Chin. Sci. Bull., 2005, 50, 758–760.
8. (a) A. Milicevic and N. Raos, J. Appl. Crystallogr., 2010, 43, 42–47.
9. (a) J. Liu, C. Guo, Z. Zhang, T. Jiang, H. Liu, J. Song, H. Fan and B. Han, Chem. Commun., 2010, 46, 5770–5772.

---

Footnote

† Electronic supplementary information (ESI) available: Experimental, FT-IR, XRD, TGA and proton NMR data of products. See DOI: 10.1039/c4ra12151a

---