Oxovanadium(V)-Catalyzed Synthesis of Ureas from Disilylamines and Carbon Dioxide under Ambient Pressure

Abstract

Here, a commercially available easy-to-handle oxovanadium(V) compound is demonstrated to serve as an efficient catalyst for the synthesis of ureas from disilylamines and carbon dioxide under ambient pressure. The catalytic activation of carbon dioxide proceeds without any additives, demonstrating a broad substrate scope and easy scalability to validate this catalytic activation of carbon dioxide. This catalytic system can be applied to the synthesis of unsymmetric ureas and chiral urea with retention of chirality.

Introduction

Carbon dioxide is a non-toxic, abundant, and green carbon resource. The development of methodologies for the transformation of carbon dioxide as a C1 building block into valuable compounds is of fundamental importance for the future sustainable society.¹ Catalytic activation of carbon dioxide under ambient pressure is considered to be essential for developing sustainable chemical transformations. Ureas are among the most important carbonyl compounds widely used as pesticides, herbicides, and raw materials for resins. Catalytic systems for the synthesis of ureas from amines and carbon dioxide under ambient pressure have been limited to the CsOH/ionic liquid,² TBA₂[WO₄],³ and DMAP (4-dimethylaminopyridine)⁴ systems, which use an expensive ionic liquid as a solvent or lack substrate versatility. We have recently developed the catalytic carbon dioxide activation system under ambient pressure for the synthesis of ureas from amines (Scheme 1a).⁵ This catalytic system, which was not so effective for aniline derivatives, required the use of an air-sensitive oxovanadium(V) catalyst, 3A MS as a dehydrating reagent, and N,N-diisopropylethylamine as a base, necessitating the development of more practical alternatives. The utilization of disilylamine as a substrate is envisioned to prevent the generation of water, which might cause catalyst deactivation, and the need for the addition of a base. Despite these advantages, no method has been reported to date for the catalytic synthesis of ureas using disilylamines as substrates and carbon dioxide under ambient pressure, although the reaction of silylamide complexes with carbon dioxide has been performed.⁶ A few systems for the synthesis of ureas from silylamines and carbon dioxide have been reported, but they generally require high carbon dioxide pressure or supercritical carbon dioxide.⁷ From these points of view, we set out to develop a practical catalytic process for the synthesis of ureas from disilylamines and carbon dioxide under ambient pressure by using a commercially available easy-to-handle oxovanadium(V) compound (Scheme 1b).

Scheme 1. Oxovanadium(V)-Catalyzed Synthesis of Ureas from Carbon Dioxide.

Results and Discussion

We initially conducted a study to check whether oxovanadium(V) compounds could act as catalysts for activation of carbon dioxide (supplied by CO₂ balloon) in the synthesis of ureas from disilylamines. 2-Phenylethyl-N,N-bis(trimethylsilyl)amine (1a) was chosen as the disilylamine for product identification. The oxovanadium(V) compound, VO(OⁱPr)₃, which was effective in the catalytic transformation of various primary amines into the ureas with carbon dioxide,⁵ facilitates the catalytic transformation of 1a with carbon dioxide into the corresponding urea 2a in 68% yield in the absence of 3A MS (Table 1, entry 1). In the previous report,⁵ 3A MS was required to remove the generated water. In the present system, the catalytic reaction proceeded even without the presence of 3A MS because hexamethyldisiloxane might be generated as a byproduct. Encouraged by this result, the efficiency of oxovanadium(V) compounds was screened. A commercially available easy-to-handle NH₄VO₃ was found to perform excellent catalytic activity, affording 2a in 95% yield (entry 2). The control experiment showed that the oxovanadium(V) catalyst is indispensable for this catalytic transformation of carbon dioxide (entry 3). The catalytic reaction with VO(TEA)⁸ instead of NH₄VO₃ proceeded well to give 2a in a good yield (entry 4). Using V₂O₅, the corresponding urea 2a was also obtained, albeit in a lower yield (entry 5). Tetravalent oxovanadium(IV) compounds such as VOSO₄·nH₂O and VO(acac)₂ exhibited moderate catalytic activities (entries 6 and 7). Catalytic activities of transition-metal oxides other than oxovanadium compounds were also examined. In this paper, TiO₂, NbO₂, Nb₂O₅, WO₃, FeO, and Fe₂O₃ were selected, but no promising results were observed (entries 8–13).

Table 1. Metal-Catalyzed Urea Synthesis from 1a and CO₂^a.

entry	catalyst	NMR yieldb (%)
1	VO(OiPr)3	68
2	NH4VO3	95
3	―	N.D.
4	VO(TEA)c	70
5	V2O5	47
6	VOSO4·nH2O	56
7	VO(acac)2	48
8	TiO2	9
9	NbO2	2
10	Nb2O5	N.D.
11	WO3	8
12	FeO	23
13	Fe2O3	3

^aReaction conditions: 1a (0.3 mmol) and catalyst (20 mol %) in DMA (1.0 mL) under CO₂ (balloon) at 100 °C for 15 h.

^bNMR (%) = [2a (mmol) × 2/1a (mmol)] × 100.

^cVO(TEA) = .

As NH₄VO₃ was found to have a high catalytic activity, the reaction was optimized using this catalyst to improve the reaction further. First, the solvent was changed from DMA (N,N-dimethylacetamide) to other polar solvents such as DMF (N,N-dimethylformamide), DMSO (dimethyl sulfoxide), and NMP (N-methylpyrrolidone), in which carbon dioxide can be dissolved efficiently. In all cases, the yields of the desired product 2a were good but not better than that using DMA as a solvent (Table 2, entries 1–4). 1,4-Dioxane was found to be not effective in this catalytic system (entry 5). When non-polar solvents such as toluene and mesitylene were used, 2a was not obtained at all (entries 6 and 7). The desired urea 2a was not produced under neat conditions (entry 8). Next, the optimal amount of DMA was examined (entries 1 and 9–11), and 0.3 M was found to be the appropriate reaction concentration under the conditions. When the amount of catalyst loading was reduced from 20 to 8 mol %, a 16% drop in the yield was observed (entry 12). The reaction time was extended from 15 to 24 h, but no improvement of the reaction efficiency was observed (entry 13). When the reaction temperature was increased from 100 to 120 °C, the yield was improved from 79% (entry 12) to 94% isolated yield (entry 14). From the above, we concluded that the reaction conditions at entry 14 were optimal.

Table 2. NH₄VO₃-Catalyzed Urea Synthesis from 1a and CO₂^a.

entry	1a (X mmol)	NH4VO3 (Y mol %)	temperature (Z °C)	solvent	NMR yieldb (%)
1	0.3 mmol	20	100	DMA	95
2	0.3 mmol	20	100	DMF	80
3	0.3 mmol	20	100	DMSO	87
4	0.3 mmol	20	100	NMP	89
5	0.3 mmol	20	100	1,4-dioxane	N.D.
6	0.3 mmol	20	100	toluene	N.D.
7	0.3 mmol	20	100	mesitylene	N.D.
8	0.3 mmol	20	100	neat	N.D.
9	0.3 mmol	20	100	DMA (0.5 mL)	81
10	0.3 mmol	20	100	DMA (2.0 mL)	77
11	0.3 mmol	20	100	DMA (4.0 mL)	73
12	0.6 mmol	8	100	DMA	79
13	0.6 mmol	8	100	DMA	78c
14	0.6 mmol	8	120	DMA	94d

^aReaction conditions: 1a (X mmol) and NH₄VO₃ (Y mol %) in solvent (1.0 mL) under carbon dioxide (balloon) at Z °C for 15 h.

^bNMR (%) = [2a (mmol) × 2/1a (mmol)] × 100.

^cFor 24 h.

^dIsolated yield.

With the optimized reaction conditions established, the substrate scope of disilylamines was explored (Table 3). The catalytic reaction of alkyl-substituted disilylamines proceeded smoothly to afford the corresponding ureas 2a–g in good yields (entries 1–7). In the case of 2-(4-bromophenyl)ethyl-N,N-bis(trimethylsilyl)amine (1b), the corresponding urea 2b was obtained in 76% isolated yield, in which the obtained product can be utilized for further transformation using the Br group (entry 2). This catalytic system could be applied to chiral disilylamine 1g derived from (R)-(+)-1-phenylethylamine, converting into the corresponding chiral urea 2g without loss of chirality as determined by chiral HPLC analysis (entry 7).⁹ When phenyldisilylamine (entry 8) and para-substituted phenyldisilylamines (entries 9 and 10) were used, the yields slightly decreased compared with those of alkyl-substituted disilylamines (entries 1–7). The reason for the decrease in yield is probably that the bulky and electron-withdrawing phenyl group compared with the alkyl group is bonded to the nitrogen atom which coordinates to the vanadium center in the catalytic cycle. The catalytic reaction of the disilylamine consisting of a linear or cyclic alkyl group took place well to provide the corresponding ureas in good yields (entries 11–13). An ether group could be incorporated in disilylamine and did not interfere with this reaction (entry 14).

Table 3. Substrate Scope of Disilylamines in the Catalytic Synthesis of Ureas^a.

^aReaction conditions: substrate 1 (0.60 mmol) and NH₄VO₃ (8 mol %) in DMA (1.0 mL) under CO₂ (balloon) at 120 °C for 15 h.

^bIsolated yield (%) = [2 (mmol) × 2/1 (mmol)] × 100.

To demonstrate the practical utility of this catalytic system, a gram-scale catalytic reaction of 1a was performed (Scheme 2). Using 15 mol % of NH₄VO₃, 1.2 mL (4.0 mmol) of 1a reacted smoothly with carbon dioxide to yield 385 mg (72% isolated yield) of the desired urea 2a.

Scheme 2. Gram-Scale NH₄VO₃-Catalyzed Urea Synthesis of 2a.

To further evaluate the synthetic utility of the current methodology, we turned our attention toward the synthesis of unsymmetric ureas, which are important compounds for pharmaceuticals, agricultural chemicals, and materials. The reaction of 1a with carbon dioxide in the presence of 2 equiv of morpholine (3a) under the catalytic reaction conditions was found to lead to the formation of the corresponding unsymmetric urea 4aa in 60% yield with the concomitant formation of the symmetric urea 2a in 19% yield (Table 4). When 4 equiv of 3a was used, the unsymmetric urea 4aa was obtained in 71% yield. By the addition of piperidine (3b) or dibutylamine (3c), the corresponding unsymmetric ureas 4ab or 4ac were produced in good yields (60 and 67% yields, respectively). It is worth mentioning that these unsymmetric ureas were main products, although a small amount of symmetric urea was produced. To the best of our knowledge, this is the first example of the catalytic synthesis of unsymmetric ureas derived from disilylamines and carbon dioxide under ambient pressure.

Table 4. NH₄VO₃-Catalyzed Unsymmetric Urea Synthesis^a.

^aReaction conditions: substrate 1a (0.30 mmol), 3 (0.60 mmol), and NH₄VO₃ (20 mol %) in DMA (1.0 mL) under CO₂ (balloon) at 120 °C for 15 h.

^bNMR yield (%) = [4 (mmol)/1a (mmol)] × 100.

^cIsolated yield (%) = [2a (mmol) × 2/1a (mmol)] × 100.

^d1.2 mmol of 3a was used.

Conclusions

In conclusion, a commercially available easy-to-handle NH₄VO₃ was demonstrated to serve as an efficient catalyst in the catalytic utilization of carbon dioxide as a C1 building block under ambient pressure for the synthesis of ureas from disilylamines. This is the first example of the catalytic synthesis of ureas from disilylamine and carbon dioxide under ambient pressure. This catalytic system, which is convenient and easily handleable, displayed a wide range of substrate applicability without the use of any dehydrating reagent or base, including a gram-scale catalytic reaction. Another interesting feature is that this transformation can be applied to the synthesis of unsymmetric ureas and chiral urea without loss of chirality. Studies on the reaction mechanism and synthetic versatility and applications of this practical catalytic system to other reactions are now in progress.

Experimental Section

General Information

Disilylamines (1a–1g,¹⁰1h–1j,¹¹ and 1k–1n(10)) and VO(TEA)⁸ were prepared according to the literature method. The other catalysts and solvents were purchased from commercial sources and further purified by the standard methods if necessary. ¹H NMR, ¹³C NMR, ¹⁹F NMR, and ²⁹Si NMR spectra were recorded in CDCl₃, DMSO-d₆, CD₃OD, or CD₃CN on a JEOL JNM-ECS 400 MHz spectrometer. Chemical shifts of ¹H NMR and ¹³C NMR spectra were given in δ (ppm) relative to the residual solvent signal as an internal standard. Chemical shifts of ²⁹Si{¹H} NMR spectra were reported relative to the external reference Me₄Si (δ = 0 ppm). Chemical shifts of ¹⁹F{¹H} NMR spectra were referenced to an external PhCF₃ (δ = −63.7 ppm). High-resolution mass spectroscopy (HRMS) was performed on a JEOL JMS-700 spectrometer. The analysis of the chiral urea product 2g was carried out using HPLC (Chiralpak IA, hexane/CHCl₃/EtOH = 8:2:1, flow 0.5 mL/min, 254 nm).

Disilylamine 1b

¹H NMR (400 MHz, C₆D₆): δ 7.19−7.16 (m, 2H), 6.78−6.75 (m, 2H), 2.81−2.77 (m, 2H), 2.43−2.39 (m, 2H), 0.09 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 139.1, 131.9, 130.5, 120.2, 48.1, 42.0, 2.5; ²⁹Si NMR (79 MHz, C₆D₆): δ 5.19; HRMS (ESI) m/z calcd for C₁₄H₂₇BrNSi₂ ([M + H]⁺), 344.0865; found, 344.0875.

Disilylamine 1c

¹H NMR (400 MHz, C₆D₆): δ 7.21−7.15 (m, 4H), 3.16−3.08 (m, 2H), 2.81−2.73 (m, 2H), 2.36 (s, 3H), 0.35 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 137.3, 135.4, 129.5, 128.8, 48.6, 42.4, 21.2, 2.4; ²⁹Si NMR (79 MHz, C₆D₆): δ 4.96; HRMS (ESI) m/z calcd for C₁₅H₃₀NSi₂ ([M + H]⁺), 280.1917; found, 280.1917.

Disilylamine 1d

¹H NMR (400 MHz, C₆D₆): δ 7.20–7.06 (m, 5H), 2.99−2.93 (m, 1H), 2.88−2.82 (m, 1H), 2.76−2.67 (m, 1H), 1.19 (d, J = 7.1 Hz, 3H), 0.13 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 146.0, 128.7, 127.8, 126.6, 53.9, 43.9, 18.5, 2.7; ²⁹Si NMR (79 MHz, C₆D₆): δ 5.44; HRMS (ESI) m/z calcd for C₁₅H₃₀NSi₂ ([M + H]⁺), 280.1917; found, 280.1922.

Disilylamine 1e

¹H NMR (400 MHz, C₆D₆): δ 7.28–7.14 (m, 5H), 2.88−2.83 (m, 2H), 2.50 (t, J = 7.6 Hz, 2H), 1.82−1.73 (m, 2H), 0.21 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 142.2, 128.7, 128.6, 126.1, 45.6, 37.6, 34.0, 2.4; ²⁹Si NMR (79 MHz, C₆D₆): δ 4.76; HRMS (ESI) m/z calcd for C₁₅H₃₀NSi₂ ([M + H]⁺), 280.1917; found, 280.1917.

Disilylamine 1g

¹H NMR (400 MHz, C₆D₆): δ 7.39–7.08 (m, 5H), 4.30 (q, J = 7.1 Hz, 1H), 1.50 (d, J = 7.1 Hz, 3H), 0.11 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 147.7, 128.2, 127.1, 126.3, 53.2, 23.3, 3.6; ²⁹Si NMR (79 MHz, C₆D₆): δ 4.13; elemental analysis (%) calcd for C₁₄H₂₇NSi₂: C, 10.25; H, 63.32; N, 5.27; found: C, 10.32; H, 63.14; N, 5.33%.

Disilylamine 1i

¹H NMR (400 MHz, C₆D₆): δ 7.02−6.98 (m, 2H), 6.88−6.83 (m, 2H), 2.73 (sept., J = 7.1 Hz, 1H), 1.15 (d, J = 7.1 Hz, 6H), 0.11 (s, 18H); ¹³C NMR (100 MHz, C₆D₆): δ 145.7, 144.3, 130.3, 126.8, 33.9, 24.4, 2.4; ²⁹Si NMR (79 MHz, C₆D₆): δ 3.55; HRMS (ESI) m/z calcd for C₁₅H₃₀NSi₂ ([M + H]⁺) 280.1917; found, 280.1917.

General Procedure for Oxovanadium(V)-Catalyzed Urea Synthesis

In a 10 mL two-necked flask, disilylamine 1 (0.60 mmol), NH₄VO₃ (5.6 mg, 0.048 mmol), and DMA (1.0 mL) were placed in a glovebox filled with nitrogen. Next, nitrogen in the flask was replaced with CO₂. The mixture was stirred at 120 °C for 15 h, followed by treatment with 1 M HCl aq. and extraction with CH₂Cl₂. The organic layer was dried over Na₂SO₄, filtrated, and removed under reduced pressure. Urea 2 was isolated by reprecipitation from CH₂Cl₂ and hexane or preparative TLC (ethyl acetate/CH₂Cl₂ = 1:2). 1,3,5-Trimethoxybenzene was used as an internal standard, and ¹H NMR analysis was performed to determine the NMR yield. Spectral data of the products were identical with those of authentic samples.

N,N′-Bis(2-phenylethyl)urea (2a)¹²

¹H NMR (400 MHz, CDCl₃): δ 7.32–7.16 (m, 10H), 4.17 (br, 2H), 3.44−3.39 (m, 4H), 2.79 (t, J = 6.8 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 158.1, 139.3, 129.0, 128.7, 126.5, 41.8, 36.5; HRMS (ESI) m/z calcd for C₁₇H₂₀N₂ONa ([M + Na]⁺), 291.1473; found, 291.1478.

N,N′-Bis[2-(4-bromophenyl)ethyl]urea (2b)⁵

¹H NMR (400 MHz, CDCl₃): δ 7.42 (d, J = 8.2 Hz, 4H), 7.05 (d, J = 8.2 Hz, 4H), 4.13 (br, 2H), 3.41−3.37 (m, 4H), 2.75 (t, J = 6.6 Hz, 4H); ¹³C NMR (100 MHz, CD₃OD): δ 160.9, 140.1, 132.5, 131.9, 120.9, 42.2, 36.8; HRMS (ESI) m/z calcd for C₁₇H₁₉Br₂N₂ONa ([M + Na]⁺), 446.9684; found, 446.9687.

N,N′-Bis[2-(4-methylphenyl)ethyl]urea (2c)⁵

¹H NMR (400 MHz, CDCl₃): δ 7.11–7.05 (m, 8H), 4.34 (br, 2H), 3.40–3.34 (m, 4H), 2.73 (t, J = 6.9 Hz, 4H), 2.32 (s, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 158.0, 136.09, 136.08, 129.4, 128.8, 41.8, 35.9, 21.2; HRMS (ESI) m/z calcd for C₁₉H₂₄N₂ONa ([M + Na]⁺), 319.1786; found, 319.1791.

N,N′-Bis(2-phenylpropyl)urea (2d)⁵

¹H NMR (400 MHz, CDCl₃): δ 7.30–7.14 (m, 10H), 4.24 (br, 2H), 3.43–3.35 (m, 2H), 3.14–3.05 (m, 2H), 2.90–2.80 (m, 2H), 1.21 (d, J = 7.1 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 158.1, 144.5, 128.7, 127.4, 126.6, 47.29, 47.26, 40.3, 19.3; HRMS (ESI) m/z calcd for C₁₉H₂₄N₂ONa ([M + Na]⁺), 319.1786; found, 319.1779.

N,N′-Bis(3-phenylpropyl)urea (2e)¹³

¹H NMR (400 MHz, CDCl₃): δ 7.28–7.14 (m, 10H), 4.92 (br, 2H), 3.18–3.13 (m, 4H), 2.62 (t, J = 7.6 Hz, 4H), 1.79 (quint., J = 7.6 Hz, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 158.3, 141.7, 128.5, 128.4, 126.0, 40.2, 33.3, 31.9; HRMS (ESI) m/z calcd for C₁₉H₂₄N₂ONa ([M + Na]⁺), 319.1786; found, 319.1786.

N,N′-Bis(phenylmethyl)urea (2f)^5,12

¹H NMR (400 MHz, CD₃OD): δ 7.32–7.20 (m, 10H), 4.34 (s, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 158.3, 138.9, 128.7, 127.48, 127.47, 44.7; HRMS (ESI) m/z calcd for C₁₅H₁₆N₂ONa ([M + Na]⁺), 263.1160; found, 263.1161.

N,N′-Bis[(1R)-1-phenylethyl]urea (2g)^5,7b

¹H NMR (400 MHz, CDCl₃): δ 7.28–7.11 (m, 10H), 4.78−4.73 (m, 2H), 4.55 (br, 2H), 1.39 (d, J = 6.9 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 156.8, 144.1, 128.8, 127.3, 125.8, 50.4, 23.5; HRMS (ESI) m/z calcd for C₁₇H₂₀N₂ONa ([M + Na]⁺), 291.1473; found, 291.1487.

N,N′-Diphenylurea (2h)¹⁴

¹H NMR (400 MHz, DMSO-d₆): δ 8.64 (br, 2H), 7.42−7.39 (m, 2H), 7.26−7.21(m, 2H), 6.95−6.90 (m, 1H); ¹³C NMR (100 MHz, DMSO-d₆): δ 153.1, 140.2, 129.3, 122.3, 118.7; HRMS (EI) m/z calcd for C₁₃H₁₂N₂ONa ([M + Na]⁺), 235.0847; found, 235.0831.

N,N′-Bis(4-isopropylphenyl)urea (2i)¹⁵

¹H NMR (400 MHz, DMSO-d₆): δ 8.73 (br, 2H), 7.32 (d, J = 8.5 Hz, 4H), 7.10 (d, J = 8.5 Hz, 4H), 2.78 (sept., J = 7.1 Hz, 2H), 1.14 (d, J = 7.1 Hz, 12H); ¹³C NMR (100 MHz, CDCl₃): δ 153.7, 145.5, 135.5, 127.4, 122.0, 33.7, 24.1; HRMS (ESI) m/z calcd for C₁₉H₂₄N₂ONa ([M + Na]⁺), 319.1786; found, 319.1782.

N,N′-Bis(4-trifluoromethylphenyl)urea (2j)⁵

¹H NMR (400 MHz, CDCl₃): δ 7.60 (d, J = 8.5 Hz, 4H), 7.53 (d, J = 8.5 Hz, 4H), 6.66 (br, 2H); ¹³C NMR (100 MHz, DMSO-d₆): δ 152.1, 143.1, 126.2 (q, ³J_F–C = 3.8 Hz), 124.6 (q, ¹J_F–C = 271.3 Hz), 122.1 (q, ²J_F–C = 32.0 Hz); ¹⁹F NMR (377 Hz, DMSO-d₆): δ −63.0; HRMS (EI) m/z calcd for C₁₅H₉F₆N₂O ([M]⁻), 347.0619; found, 347.0623.

N,N′-Dihexylurea (2k)¹²

¹H NMR (400 MHz, CDCl₃): δ 4.50 (br, 2H), 3.16–3.11 (m, 4H), 1.51–1.43 (m, 4H), 1.34–1.25 (m, 12H), 0.87 (t, J = 6.8 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 159.2, 40.7, 31.7, 30.3, 26.7, 22.7, 14.1; HRMS (ESI) m/z calcd for C₁₃H₂₈N₂ONa ([M + Na]⁺), 251.2099; found, 251.2093.

N,N′-Didecylurea (2l)¹⁶

¹H NMR (400 MHz, CDCl₃): δ 4.20 (br, 2H), 3.16–3.12 (m, 4H), 1.52–1.45 (m, 4H), 1.29–1.25 (m, 28H), 0.88 (t, J = 6.9 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 158.3, 40.9, 32.0, 30.3, 29.72, 29.70, 29.48, 29.46, 27.0, 22.8, 14.3; HRMS (ESI) m/z calcd for C₂₁H₄₄N₂ONa ([M + Na]⁺), 363.3351; found, 363.3340.

N,N′-Dicyclohexylurea (2m)¹²

¹H NMR (400 MHz, CDCl₃): δ 4.07 (br, 2H), 3.50–3.43 (m, 2H), 1.95−1.90 (m, 4H), 1.71−1.49 (m, 6H), 1.39−1.29 (m, 4H), 1.19−1.07 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 157.1, 49.6, 33.8, 25.6, 25.0; HRMS (ESI) m/z calcd for C₁₃H₂₄N₂ONa ([M + Na]⁺), 247.1786; found, 247.1784.

N,N′-Bis(3-ethoxypropyl)urea (2n)⁵

¹H NMR (400 MHz, CDCl₃): δ 4.86 (br, 2H), 3.52–3.44 (m, 8H), 3.27 (t, J = 6.3 Hz, 4H), 1.79–1.73 (m, 4H), 1.20 (t, J = 7.1 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 158.6, 69.2, 66.5, 39.1, 30.0, 15.4; HRMS (ESI) m/z calcd for C₁₁H₂₄N₂O₃Na ([M + Na]⁺), 255.1685; found, 255.1691.

N-(2-Phenylethyl)-4-morpholinecarboxamide (4aa)¹⁷

¹H NMR (400 MHz, CDCl₃): δ 7.33–7.19 (m, 5H), 4.44 (br, 1H), 3.67−3.65 (m, 4H), 3.53−3.49 (m, 2H), 3.29−3.26 (m, 4H), 2.83 (t, J = 6.9 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 157.8, 139.4, 128.9, 128.7, 126.6, 66.6, 44.0, 42.1, 36.4; HRMS (ESI) m/z calcd for C₁₃H₁₈N₂O₂Na ([M + Na]⁺), 257.1266; found, 257.1272.

N-(2-Phenylethyl)-1-piperidinecarboxamide (4ab)¹⁸

¹H NMR (400 MHz, CDCl₃): δ 7.32–7.18 (m, 5H), 4.47 (br, 1H), 3.50−3.45 (m, 2H), 3.27−3.24 (m, 4H), 2.82 (t, J = 7.0 Hz, 2H), 1.60–1.48 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 157.7, 139.7, 129.0, 128.6, 126.4, 44.9, 42.2, 36.5, 25.7, 24.5; HRMS (ESI) m/z calcd for C₁₄H₂₀N₂ONa ([M + Na]⁺), 255.1473; found, 255.1478.

N,N-Dibutyl-N′-(2-phenylethyl)urea (4ac)

¹H NMR (400 MHz, CDCl₃): δ 7.32–7.19 (m, 5H), 4.23 (br, 1H), 3.51−3.47 (m, 2H), 3.10−3.07 (m, 4H), 2.83 (t, J = 6.8 Hz, 2H), 1.45−1.37 (m, 4H), 1.23 (sext., J = 7.3 Hz, 4H), 0.88 (t, J = 7.3 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 157.7, 139.7, 129.0, 128.7, 126.5, 47.2, 42.0, 36.4, 30.8, 20.3, 14.0; HRMS (ESI) m/z calcd for C₁₇H₂₈N₂ONa ([M + Na]⁺), 299.2099; found, 299.2105.

Procedure for Gram-Scale NH₄VO₃-Catalyzed Urea Synthesis of 2a

In a 10 mL two-necked flask, 2-phenylethyl-N,N-bis(trimethylsilyl)amine (1a) (1.2 mL, 4.0 mmol), NH₄VO₃ (70.2 mg, 0.60 mmol), and DMA (6.0 mL) were placed in a glovebox filled with nitrogen. Next, nitrogen in the flask was replaced with CO₂. The mixture was stirred at 120 °C for 48 h, followed by treatment with 1 M HCl aq. and extraction with CH₂Cl₂. The organic layer was dried over Na₂SO₄, filtrated, and removed under reduced pressure. The residue was isolated by reprecipitation from CH₂Cl₂ and hexane to give 385 mg (72% yield) of N,N′-bis(2-phenylethyl)urea (2a).

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c07367.

• ¹H NMR, ¹³C NMR, ¹⁹F NMR, and ²⁹Si NMR spectral data and HPLC charts (PDF)

The authors declare no competing financial interest.