Selective N-Alkylation of Amines with DMC over Biogenic Cu–Zr Bimetallic Nanoparticles

Abstract

Herein, we report the green synthesis of copper–zirconium bimetallic nanoparticles (Cu–Zr BNPs) from aqueous solutions using Azadirachta indica leaf extract as a reducing and stabilizing agent. The CuO, ZrO₂ NP, and Cu–Zr BNP samples were characterized by X-ray diffraction and Fourier transform infrared (FTIR) spectroscopy, and the morphologies of the samples were analyzed by high-resolution transmission electron microscopy (HR-TEM) with selected area electron diffraction analysis (SAED). The synthesized Cu–Zr BNPs have been employed as efficient catalysts for the selective N-methylation of aromatic and aliphatic amines with dimethyl carbonate. The effect of process conditions on the percentage conversion of benzylamine with dimethyl carbonate as a model reaction has been investigated. The Cu–Zr bimetallic nanoparticle catalytic system in a 1:2 molar ratio was able to convert amines into the corresponding N-methylated amines with a selectivity up to 91% at 180 °C in 4 h. The analysis of catalytic reusability confirmed that the reported heterogeneous catalyst can be used for five consecutive cycles without much loss in activity. Thus, the current protocol can be considered as a simpler, reproducible, and environmentally benign approach for N-methylation of amines.

Introduction

Alkylamines are compounds of great interest because of their widespread use and applications as intermediates or as a whole in biology and medicine disciplines, in addition to chemistry.¹⁻⁴ A number of top-selling drugs such as Olanzapine, Oxycodone, Imatinib, Viagra, and Venlafaxine contain N-methylamino groups (Figure 1).

Figure 1.

Structures of some pharmacologically important compounds with N-methyl moiety.

Alkylamines are often prepared by carrying alkylation of lower amines with alkyl halides⁵ or dimethyl sulfate.⁶ These reagents, apart from being toxic, also lead to the generation of stoichiometric amounts of halides and sulfate wastes (Scheme 1). Moreover, there exists the problem with selectivity, due to overalkylation of the amine obtained.^7,8 Thus, it has remained a great challenge for the scientific community to develop alkylating methodologies that are environmentally benign and able to deliver the desired N-alkylated amine selectively besides others. A number of routes have been employed recently for the aforesaid purpose. Two most common and extensively worked-upon methods among them include methylation using alcohols⁹ and dialkyl carbonates¹⁰ as carbon sources. Both of them have their own range of benefits and limitations. The H-borrowing methodology employing alkylation of amines using methanol as a carbon source has been explored extensively, in the presence of a wide array of heterogeneous catalysts.¹¹⁻¹⁴N-alkylation with dialkyl carbonates, on the other hand, is considered an environmentally benign method since the alkylation reaction releases methanol and carbon dioxide as byproducts. Moreover, dialkyl carbonates are inexpensive, biodegradable, and excellent solvents and also possess lower toxicity and bioaccumulation.¹⁵ The only issue limiting the use of dialkyl carbonates as alkylating agents is their considerably lower reactivity than alkyl halides and dimethyl sulfates at moderate temperatures.¹⁶ This issue has been addressed by the conjunction of a suitable catalyst with dialkyl carbonates, which besides enhancing their reactivity, also increases product selectivity. To date, a variety of bases,¹⁷ transition-metal catalysts,^10,18 and metal–organic frameworks^19,20 have been used for the alkylation of different amines using dialkyl carbonates as alkylating agents. These catalysts serve to enhance the nucleophilic character of dialkyl carbonates generating preferentially alkylated products over carbamoylated product or alkylated carbamoylated product.²¹ However, the processes involving these heterogeneous catalysts too suffer from limitations such as a need of co-catalysts, postprocess catalyst separation, and high cost. Thus, developing an easily recoverable and recyclable heterogeneous catalyst for the selective N-alkylation reaction still remains a challenging task.

Scheme 1. Methodologies for the Synthesis of N-Methylated Amines.

Bimetallics is another category of catalysts, which have also been used as catalysts toward the generation of dimethyl carbonate (DMC) from CO₂ and methanol.^22,23 Bimetallization not only enhances the stability and surface area of monometallic nanoparticles (NPs) but also enhances their catalytic behavior significantly, maybe due to synergism.²⁴ Because of this, a number of bimetallic combinations like Ag–Au-, Ni–Mn-, Pd–Rh-, and Au–Cu-alloyed NPs have been utilized in p-nitrophenol reduction, thermal decomposition of ammonium perchlorate, and Suzuki coupling.²⁵⁻²⁸

Wang and co-workers recently reported an efficient photocatalytic method²⁹ for the N-methylation of heterocyclic amines using methanol with Pd/TiO₂ bimetallics under mild reaction conditions. Risi and co-workers developed a Ru nanoparticle–nanomicelle³⁰ as an effective and recyclable catalyst for the secondary amine synthesis in water. Fewer reports have been published on the use of metal oxides in N-alkylation using DMC as the alkylation source.³¹ However, none of the reports correspond to the use of bimetallic nanoparticles in this reaction.

Herein, for the first time, we report a Cu–Zr bimetallic catalytic system for the selective transformation of aromatic and aliphatic amines into the corresponding N-methylated amines using DMC as the alkylation source. Biogenically synthesized bimetallic conjugate NPs have been employed as catalysts in the N-alkylation of amines. A variety of amine substrates have been converted to secondary and tertiary amines without isolation of any carbamoylated products.

Results and Discussion

Cu–Zr bimetallic nanoparticles (BNPs) have been synthesized using the simultaneous reduction methodology. The reduction of a mixture of CuSO₄·5H₂O and ZrOCl₂ solutions at varying molar ratio (Table 1) was carried out in the presence of Azadirachta indica leaf extract, to generate Cu–Zr BNPs in excellent yields. The bioextract has been obtained by boiling the leaves of A. indica in deionized water and utilizing it as such for reduction. The terpenoid and flavanone phytochemicals present in the Azadirachta leaf extract acts both as a reducing and capping agent, thus helping in stabilizing nanoparticles.³² The nanoparticles obtained were found to be quite stable as no aggregation took place even after a week, as reflected in the high-resolution transmission electron microscopy (HR-TEM) images (Figure S1a,b).

Table 1. Efficacy of Nanoparticles toward N-Methylation of Benzylamine with DMC^a.

		% yield (products)b
entry	catalyst	N-methylatedc	N-carbamoylated
1	CuO	15	52
2	ZrO2	72	18
3	Cu–Zr (1:1); 1a	49	16
4	Cu–Zr (2:1); 1b	54	21
5	Cu–Zr (1:2); 1c	83	07

^aBenzylamine (30 mmol), DMC (100 mmol), catalyst (20 mol %), reaction conditions: 180 °C, 4 h, N₂.

^bGas chromatography (GC) yield.

^cYield of mono- and dimethylated products as a whole.

Bimetallic Nanoparticle Characterization

The as-synthesized NPs have been characterized as below.

Fourier Transform Infrared (FT-IR) Spectroscopy

The FT-IR spectra of CuO NPs, ZrO₂ NPs, and Cu–Zr BNPs have been recorded in the range 400–4000 cm^–1 (Figure 2). The FTIR spectrum for the Azadirachta leaf extract (Figure 2) shows major peaks in the region 3500–3300 and 2933 cm^–1 (phenolic group and C–H peak stretching); the peak at 1603 cm^–1 corresponds to the stretching frequency of the C=O group. The presence of the methoxy group can be correlated with a stretching peak at 1021 cm^–1. A strong peak at 632 cm^–1 in the ZrO₂ NP sample corresponds to the Zr–O stretching vibration,³³ while in CuO nanoparticles, the stretching frequency in the region 3600–3100 cm^–1 might be due to the O–H groups of the extract components. Two more peaks at 2900 and 1750 cm^–1 correspond to C–H asymmetric stretching and C=O stretching frequency. The bands at 1640 and 1500 cm^–1 are due to aromatic C=C stretching, and the peak at 1059 cm^–1 might be due to C–OH bending,³⁴ The bimetallic Cu–Zr sample displayed the characteristic peaks of both the components. The peaks at 3600–3300 cm^–1 (O–H stretching), 1621 cm^–1 (C=O stretching), and 655 cm^–1 (Zr–O stretching) are more prominent among other small peaks.

Figure 2.

FTIR spectra of plant extract, CuO, ZrO₂, and Cu–Zr nanoparticles.

The significant reduction in the intensity of hydroxyl and carbonyl groups in the infrared (IR) spectrum of BNPs suggested that these functional groups might be involved in the reduction of the metal ions. Besides this, the presence of other stretching frequencies (corresponding to organic functional groups) suggested that the NPs were capped with biomolecules from the Azadirachta leaf extract, and hence are stable.

X-ray Diffraction (XRD)

XRD patterns of CuO, ZrO₂ NPs, and Cu–Zr BNPs are shown in Figure 3. The observed planes of pure ZrO₂ are associated with (101), (110), (112), and (211) at 2θ = 30.2, 35.3, 50.5, and 60.2°, respectively, with JCPDS card number 80-0965. These planes are associated with d-spacing values of 2.9, 2.5, 1.8, and 1.5 Å, respectively, and can be promptly allotted to the tetragonal structure, similar to that of bulk t-ZrO₂ reported previously.³⁵ For CuO NPs, diffraction peaks are observed at 2θ = 8.2, 23.6, 25.7, 39.1, and 43.6° with (−101), (−213), (−121), (204), and (−612) planes, respectively. These planes are then associated with d-spacing values of 11.4, 3.7, 3.4, 2.3, and 2.0 Å with JCPDS card number 96-702-9163 and readily assigned to the monoclinic structure of CuO NPs. Zr has a board peak in Cu–Zr BNPs at Bragg’s angle 30.2°, which corresponds to the (101) reflection. The full width at half-maximum (FWHM) of the most intense peak at the 2θ position was calculated with the Scherer equation.³⁶ On average, the crystallite sizes of the prepared CuO, ZrO₂, and Cu–Zr NPs were found to be 16.8, 10.5, and 14.6 nm, respectively. There are some unidentified peaks in the XRD pattern of Cu–Zr BNPs maybe due to the crystallization of biomolecules of the A. indica leaf extract.

Figure 3.

XRD spectra of CuO, ZrO₂, and Cu–Zr BNPs.

High Resolution Transmission Electron Microscopy

HR-TEM was used to better describe the size, morphology, and structure of the resulting Cu–Zr BNPs. Figure 4a–c displays the Cu–Zr BNPs TEM images with a different scale bar (10, 5, and 2 nm) to check the morphology of the nanoparticles. To visualize the lattice fringes of the structure, a specific area with two typical regions has been selected (Figure 4b,c). As observed in Figure 4d, the lattice fringes with an interplanar spacing of about 0.29 nm associated with the (110) lattice spacing correspond to the ZrO₂ matrix. Further, in Figure 4e, the structure of CuO with an interplanar spacing of 0.34 nm is observed, which is due to the (−121) plane of orientation of lattice. The selected area electron diffraction (SAED) pattern (Figure 4f) has confirmed the crystalline nature of the as-synthesized material. The presence of quasi-ring-like diffraction pattern demonstrating the polycrystalline structure and the (−121), (204), (112), and (211) rings were indexed to the tetragonal and monoclinic structure of ZrO₂ and CuO NPs, which are in good agreement with XRD results. To further determine the composition of sheetlike Cu–Zr composites, energy-dispersive X-ray spectroscopy (EDS) was carried out as shown in Figure 4g. The obtained spectrum suggests the existence of four elements Cu, Zr, S, and O.

Figure 4.

(a–e) HR-TEM images, (f) SAED pattern, and (g) EDS spectra of Cu–Zr BNPs.

Brunauer–Emmett–Teller (BET) Adsorption Studies

The N₂ adsorption/desorption isotherm analysis has been carried out to give further understanding into the textural properties of CuO/ZrO₂ BNPs. Typical IV isotherms with H3 hysteresis loops characteristic of mesoporous materials were observed (Figure S2). The specific surface area and mean pore diameter observed from BET were found to be 30.4 m²/g and 14.5 nm, respectively.

N-Methylation of Amines

The catalytic activity of the prepared Cu–Zr BNPs has been evaluated toward the N-methylation of amines with DMC. As a model reaction, N-methylation of benzylamine was carried out with excess DMC in the presence of various mono- and bimetallic NPs. The reaction was performed under autoclave conditions at 150 °C for 4 h with 20 mol % of the catalyst, and the results are reported in Table 1.

Both N-methylated and N-carbamoylated products were obtained in varying ratios, with mono- and bimetallic NPs (Table 1). However, it can be inferred from Table 1 that carbamoylation of amines was preferred over methylation in the presence of CuO NPs (entry 1), while the methylated product dominated with ZrO₂ NPs (entry 2). The results obtained are clearly in agreement with those reported in the literature.³⁷ On the contrary, with bimetallic NPs, both the products were isolated under similar conditions. Best yields of methylated products (82% of mono- and dimethylated and 15% of carbamoylated products) were obtained with Cu–Zr combined in a 1:2 ratio (entry 5, Table 1). Further, since a high temperature favors the formation of methylated products over others, which may be due to the decomposition of carbamoylated product to methylated product,²¹ the same reaction was performed at higher temperatures to increase the selectivity of products toward alkylation. It was observed that at lower temperatures (90–120 °C), the yields of the methylated components were found to be low even with excess of DMC (Figure 5). A rise in temperature up to 150–180 °C increased the yields of mono- and dimethylated products. A further increase in temperature to 210 °C leads only to a minor change in the yields of dimethylated product. Further, the reaction conditions were optimized with respect to catalytic dosage and reaction duration, and the results obtained are summarized in Table 2. As is clear from Table 2 (entries 8, 9, 13, and 14), the yield of mono- and dimethylated products is highest after 3–4 h. Thus, an optimum catalyst dosage of 20%, a temperature of 180 °C, and a reaction time of 4 h were chosen for further synthesis.

Figure 5.

Influence of temperature on N-methylation of amines with DMC in the presence of Cu–Zr bimetallic NPs; reaction conditions: benzylamine, 30 mmol; DMC, 100 mmol; catalyst, 20 mol %.

Table 2. Optimization of Reaction Conditions for N-Methylation of Benzylamine^a.

			% yieldb
sl. no.	catalyst loading (mol %)	duration (min)	monosubstituted product	disubstituted product
1	10	60	18
2	10	120	23
3	10	180	27
4	10	240	30	9
5	10	overnight	33	11
6	20	60	37
7	20	120	42	07
8	20	180	55	19
9	20	240	56	25
10	20	overnight	53	32
11	30	60	38
12	30	120	43	10
13	30	180	54	15
14	30	240	61	23
15	30	overnight	56	35

^aGC yield.

^bBenzylamine (30 mmol); DMC (100 mmol); temperature, 180 °C.

With optimized reaction conditions in hand, N-methylation of differently substituted aliphatic and aromatic amines was carried out, to explore the substrate scope of the reaction, and the results are summarized in Table 3.

Table 3. N-Methylation of Amines with DMC in the Presence of Cu–Zr Bimetallic Nanoparticles^a.

		selectivity (%)
sl. no.	amine	monomethylated product	dimethylated product	carbamoylated product
1	benzylamine	66	25	5.9
2	n-butylamine	55	23	13
3	1,6-hexandiamine	45	19	17
4	cyclohexylamine	61	19	11
5	aniline	67	23	5.8
6	p-toluidine	65.4	22	5.3
7	p-anisidine	67	17.2
8	p-aminophenol	63.7	21.3

^aAmine (30 mmol), DMC (100 mmol), catalyst (20 mol %), 180 °C, 4 h.

With all of the amines under study, both mono- and di-N-substituted products were isolated with a minor amount of carboxymethylated product, as judged by GC analysis. The percentage selectivity of N-methylated products is reported in Table 3. Thus, the Cu–Zr BNP catalytic system in a molar ratio of 1:2, employed in the present study, served to achieve selectivity of up to 91% (Table 3, entry 6) toward N-methylation over carbamoylation, in reaction of the amines with DMC.

Mechanistic Details

The coordination of DMC to Zr⁴⁺ has been reported to activate carbonyl and O–CH₃ functional moieties of the DMC, and thus it promotes both the methylation and carbomethoxylation of the amine involved.^21,37 By combining the NPs of Zr⁴⁺ with Cu²⁺, the selectivity toward N-methylation enhanced as presented in Table 3. Thus, the tentative mechanism followed during the reaction can be described as per Scheme 2. The catalyst promoted the B_Al² pathway over the B_Ac² pathway, thereby increasing the extent of N-methylation in comparison to N-carboxymethylation. Moreover, high temperature causes the decarboxylation of carboxymethylated product, ultimately leading to N-methylated as the major product.²¹

Scheme 2. Proposed Mechanism for the Catalytic Role of Bimetallics in N-methylation of Amines with DMC.

Reusability of Catalyst

At the end of the protocol, the reusability of the recovered Cu–Zr bimetallic heterogeneous catalyst for the reaction of benzylamine with DMC was investigated for five consecutive cycles. The catalyst recovered upon filtration of the reaction mixture was washed with water several times and dried in an air oven at 100 °C for 4 h and calcined at 150 °C, prior to reuse. The catalyst showed only a slight and gradual decrease in its activity after every cycle, with benzylamine conversions for the five consecutive reactions being 91, 90, 89, 87, and 85% with minor variations in product distribution (Figure 6).

Figure 6.

Percentage conversion of benzylamine obtained for five consecutive runs in the presence of Cu–Zr heterogeneous catalyst.

Conclusions

In summary, a selective and efficient conversion of amines into higher amines in the presence of Cu–Zr bimetallic nanoparticles is presented here. In the presence of the proposed heterogeneous catalyst, a number of primary amines underwent methylation reaction preferentially, with dimethyl carbonate over carbamoylation. The best selectivity that could be achieved in this reaction toward methylation was 91% with the Cu–Zr bimetallic nanoparticle catalytic system in a 1:2 molar ratio. The protocol utilized DMC as a green methylating reagent as well as solvent. The heterogeneous catalyst could be easily recovered and reused multiple times without much loss in activity. Subsequently, the current protocol can be considered as a simpler, reproducible, and environmentally benign approach for N-methylation, in particular.

Experimental Section

Materials

The chemicals used in the present study were of analytical grade. Copper sulfate (CuSO₄·5H₂O) and zirconium oxychloride (ZrOCl₂) were purchased from Loba Chemicals and used without any prior purification. A. indica leaves were collected from Fatehgarh Sahib, Punjab, India. Completely washed leaves (100 g) were cut and powdered in an electrical grinder and boiled in 100 mL of deionized water for 15 min in a heating mantle. The bioextract obtained upon filtration was stored in a refrigerator (5–10 °C) prior to use.

Characterization

Fourier transform infrared (FTIR) spectra of the A. indica leaf extract, CuO NPs, ZrO₂ NPs, and Cu–Zr NPs were recorded on an FTIR Nicolet 5700 spectrometer, Thermo Corporation. The powder X-ray diffraction (XRD) studies were carried out using a Siemens D5000 X-ray diffractometer using Cu Kα radiation of wavelength 0.15418 nm. HR-TEM images of nanoparticles were recorded on a JEOL JSM-7500F HR-TEM at a 5 kV accelerating voltage. Samples prepared for HR-TEM were analyzed for elemental analysis using EDS detector attachment (Oxford Instruments software Aztec.) for the JEOL JSM-7500F at a 20 kV accelerating voltage. Monitoring of reaction progress was done using silica gel-G254 thin-layer chromatography, in which the spots were visualized in an iodine chamber. Isolation and purification of products were done through column chromatography over 60–120 mesh-sized silica gel with the hexane–ethylacetate mixture as an eluent. The nanoparticles of heterogeneous catalysts were placed under vacuum for 1 h at 393 K for drying, before use. Nuclear magnetic resonance (NMR) spectral analysis was performed on a 500 MHz Bruker Avance-II FTNMR spectrophotometer using CDCl₃, and the chemical shifts were recorded with respect to tetramethylsilane (TMS). The gas chromatographs were recorded on a Shimadzu GC-MS model QP-2010 plus with an RTX-1MS capillary column (30 m × 0.25 mm ID × 0.25 μm). The physical adsorption parameters like surface area and pore size were determined by the Brunauer–Emmett–Teller (BET) method.

Synthesis of CuO and ZrO₂ Nanoparticles Using A. indica Leaf Extract

The CuO and ZrO₂ NPs were prepared by biogenic reduction using plant extract.³⁸ For the synthesis of CuO NPs, 5 mL of A. indica leaf extract was added to 50 mL of 0.5 M CuSO₄·5H₂O solution in a 250 mL flask and the contents were gradually heated to 60 °C with continuous stirring till a color change was observed. Centrifugation of the mixture at 12 000 rpm for 15 min provided CuO NPs. The NPs thus obtained were dried in an oven at 80 °C prior to use. The synthesis of ZrO₂ NPs was performed in a similar way.

Synthesis of Bimetallic Nanoparticles Using A. indica Leaf Extract

Cu–Zr bimetallic NPs were synthesized by the simultaneous reduction methodology, where 10 mL of the A. indica leaf extract was added to a mixture of 25 mL of CuSO₄·5H₂O and 25 mL of ZrOCl₂ solution taken in different molar ratios (1:1, 0.5:1, and 1:0.5). The initial color of the mixture was noted. The resulting mixture was gradually heated to 60 °C and continuously stirred for 24 h on a heating cum magnetic stirrer, till a color change was observed. Centrifugation of the mixture provided Cu–Zr bimetallic NPs, which were separated by filtration and washed multiple times with distilled water to remove the unreacted components. The NPs thus obtained were dried in an oven at 80 °C for 4 h and then calcined at 150 °C, prior to use.

N-Methylation of Amines Using Cu–Zr Bimetallic Nanoparticles

For N-methylation reaction, a mixture of 30 mmol of amine, 100 mmol of DMC, and 20 mol % Cu–Zr BNP catalyst was taken in a predried 100 mL round-bottom flask (RBF). The latter is equipped with a water reflux condenser and a heating oil bath mounted on a magnetic stirrer. The contents were refluxed at the requisite temperature for a duration of 4 h. DMC was taken in excess in each case, to serve as a solvent. The heterogeneous catalyst was separated by filtration on completion of the reaction (judged by thin-layer chromatography (TLC)), and a portion of the mother liquor obtained was diluted with ethylacetate and analyzed by GC. All of the N-methylated products were extracted by column chromatography using silica gel mesh size 60–120 and hexane–ethylacetate mixture as an eluent.

Spectral Data of Purified Products

N-Methyl Benzylamine

Pale yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 2.46 (s, 3H), 3.73 (s, 2H), 6.43–6.53 (m, 1H), 6.76–6.78 (m, 2H), 6.86–7.26 (m, 2H); ¹³C NMR (CDCl₃, 125 MHz): δ 31.3, 53.5, 121.8, 123.6, 125.3, 136.9.

N,N-Dimethyl Benzylamine

Faint yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 7.21–7.35 (m, 5H), 3.57 (m, 2H), 2.36 (s, 6H); ¹³C NMR (CDCl₃, 125 MHz): δ 45.3, 63.9, 121.5, 124.1, 127.1, 139.1.

N-Benzylcarbamate

Faint yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 6.55–8.29 (m, 5H), 4.95 (br, 1H), 4.23 (s, 2H), 3.67 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ 47.2, 51.1, 122.1, 124.2, 127.6, 157.1.

N-Methylbutylamine

Pale yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 0.9 (t, 3H), 1.35 (m, 2H), 1.44 (m, 2H), 2.89 (s, 3H), 4.89 (br, 1H) 3.12 (t, 2H); ¹³C NMR (CDCl₃, 125 MHz): δ 13.7, 20.0, 32.5, 39.8.

N,N-Dimethylbutylamine

Pale yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 0.98 (t, 3H), 1.38 (m, 2H), 1.51 (m, 2H), 2.60 (s, 6H), 3.1 (t, 2H); ¹³C NMR (CDCl₃, 125 MHz): δ 13.7, 20.0, 32.5, 39.8.

N-Butylcarbamate

Pale yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 0.86 (t, 3H), 1.38 (m, 2H), 1.44 (m, 2H), 3.1 (t, 2H), 3.57 (s, 3H), 4.9 (br, 1H); ¹³C NMR (CDCl₃, 125 MHz): δ 18.8, 21.7, 28.7, 50.8, 156.2.

N,N-Dimethylhexane-1,6-iamine

White solid. ¹H NMR (CDCl₃, 500 MHz): δ 5.0 (br, 1H), 3.7 (s, 3H), 3.2 (t, 4H), 1.34 (m, 4H), 1.48 (m, 4H); ¹³C NMR (CDCl₃, 125 MHz): δ 26.1, 29.8, 45.3, 51.8.

N-Methylcyclohexylamine

White liquid. ¹H NMR (CDCl₃, 500 MHz): δ 4.77 (br, 1H), 2.7 (s, 3H), 2.08 (m, 1H), 1.93 (m, 2H), 1.72 (m,2H), 1.69 (m, 2H), 1.60 (m, 2H), 1.25 (m,1H); ¹³C NMR (CDCl₃, 125 MHz): δ 26.57, 27.04, 27.45, 33.45, 51.87, 52.42.

N-Cyclohexylcarbamate

White solid. ¹H NMR (CDCl₃, 500 MHz): δ 1.1–1.9 (m, 10H), 3.47 (s, 1H), 3.64 (s, 3H), 4.54 (br, NH); ¹³C NMR (125 MHz, CDCl₃): δ 24.7, 25.4, 33.3, 49.7, 51.7, 156.2

N-Methylaniline

Yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 7.11 (dd, 2H), 6.5 (m, 2H), 6.6 (tt, 1H), 3.36 (br, 1H), 2.72 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ 30.7, 112.4, 117.3, 129.2, 149.4.

N,N-Dimethylaniline

Yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 7.26–7.34 (m, 3H), 7.35–7.38 (m, 2H), 2.5 (s, 6H); ¹³C NMR (CDCl₃, 125 MHz): δ 40.0, 112.5, 117.3, 129.0, 149.4.

N-Methyl-p-Toluidine

Yellow liquid. ¹H NMR (CDCl₃, 500 MHz): δ 6.9 (d, 2H), 6.4 (d, 2H), 3.46 (br, 1H), 2.73 (s, 3H), 2.1 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ 29.7, 31.3, 112.6, 117.4, 128.9, 149.1

N-Methyl-p-Anisidine

Yellow solid. ¹H NMR (CDCl₃, 500 MHz): δ 6.79–6.88 (m, 2H), 7.11–7.28 (m, 2H), 3.75 (s, 3H), 3.35 (br, 1H), 2.68 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ 30.1, 51.4, 112.5, 129.8, 148.6, 154.2.

N-Methyl-p-Aminophenol

Colorless liquid. ¹H NMR (CDCl₃, 500 MHz): δ 6.53–6.75 (dd, 2H), 7.24 (dd, 2H), 3.74 (br, 1H), 3.36 (s, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ 29.7, 55.72, 114.8, 115.4, 139.7, 152.9.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c01633.

• HRTEM images of bimetallic Cu–Zr nanoparticles; N₂ adsorption isotherm for CuO·ZrO₂ bimetallic nanoparticles; and NMR spectral data of synthesized compounds (PDF)

The authors declare no competing financial interest.