Converting urea into high value-added 2-oxazolidinones under solvent-free conditions

Abstract

Zn-modified mesoporous Mg–Al nanoplates oxides were prepared by co-precipitation and further characterized and used in the synthesis of 2-oxazolidinones from urea and epoxides under solvent-free conditions. The characterization results suggested that Zn_1.1Mg_2.0AlO_4.6, which featured more accessible active medium basic sites, were favorable for obtaining superior catalytic activity. This synthetic process is mild, convenient, simple and gives good yields up to 80%.

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1. Introduction

Carbon dioxide (CO₂) is an abundant, renewable and economical carbon resource; therefore, the direct use of CO₂ as a raw material in the chemical industry should be an ideal choice.^1–4 However, the carbon atom in CO₂ is in its most oxidized form and CO₂ itself is a relatively unreactive molecule; therefore, the activation of CO₂ normally requires the use of high energy starting materials, or techniques to shift the equilibrium to the right, e.g., by removing a compound.^5,6 Urea, which can be thought of as an activated form of CO₂, may be a more feasible option for practical applications. The manufacture of urea is a very mature industry^7–9 and its supply in China is currently exceeding demand. In this sense, using urea as feedstock to produce more valuable chemicals opens a new window for CO₂ utilization. For example, urea has already been used as a building block in the synthesis of N-carbamoyl-L-amino acids,¹⁰ carbamates,^11–14 cyclic carbonates or dialkyl carbonates,^11–13 diphenyl carbonate,^15,16 other urea derivatives^17,18 and many nitrogen-containing heterocycles.^19–26 Green chemistry can be defined as the synthesis of important chemical and biological products from readily available and inexpensive starting materials through atom economical and environmentally benign strategies. In this study, urea was used for the synthesis of 2-oxazolidinones (Scheme 1), which are important cyclic compounds in both fine chemicals and synthetic organic chemistry. They are widely used in the synthesis of pharmaceuticals, pesticides, and cosmetics.^27–29 From the economic and environmental views, the direct synthesis of 2-oxazolidinones from CO₂ and aziridines^30–33 or β-amino alcohols^34–36 is more attractive. Nevertheless, most of the currently available techniques require high pressure or high temperature or some stoichiometric dehydrating reagents. To the best of our knowledge, little work appears to have been done concerning the reaction of urea and epoxides, which could be carried out without any solvent. In such a process, urea would be used as the carbonylation and an amination agent; furthermore, it is nontoxic and has abundant resources with a lower price. Moreover, NH₃ co-produced in the reaction could easily be converted to urea by reaction with CO₂ via an already established pathway. Hence, this route can be considered a green synthesis of 2-oxazolidinones via indirect utilization of CO₂.

Scheme 1 Synthesis of 2-oxazolidinones from urea and epoxides.

In this study, Zn-modified mesoporous Mg–Al mixed oxides were prepared by calcination of Zn–Mg–Al hydrotalcite-like compounds and were found to catalyze the synthesis of 2-oxazolidinones from urea and epoxides with high efficiency. TG, XRD, BET, SEM and CO₂-TPD studies were conducted to explore the relationship between structure and performance.

2. Experimental

2.1 Catalyst preparation and characterization

Mg–Zn–Al hydrotalcites (HTMg–Zn–Al) were prepared by a co-precipitation method (see ESI†).¹³ Elemental quantitative analyses of Mg, Zn and Al were performed with a CCD-based inductively coupled plasma-atomic emission spectrometer (ICP-AES, Agilent 725-ES). The morphological structures were examined by field emission scanning electron microscopy (FE-SEM, JSM-6701F). Thermal analyses were carried out using a METTLER TG1 model. X-ray diffraction (XRD) was measured on a Siemens D/max-RB powder X-ray diffract meter. The BET surface areas of the catalysts were obtained with physisorption of N₂ using a Micromeritics ASAP 2010. The surface base properties of the catalysts were measured by temperature programmed desorption (TPD) of CO₂ and carried out on TPD flow system equipped with a TCD detector.

2.2 2-Oxazolidinones synthesis from urea and epoxides

Typically, 10 mmol epoxide, 20 mmol urea and 0.05 g catalyst were added into a stainless steel autoclave with a glass tube inside. The reactions were carried out at 120–150 °C for 2–8 h with stirring. After reaction, the autoclave was cooled down to room temperature. The reaction mixture was diluted with methanol to 15 ml and then qualitatively identified by HP-7890 GC-MS, equipped with a SE-54 capillary column. Quantitative analysis of the product was carried out using an Agilent 7890 GC equipped with a SE-54 capillary column and a FID detector (biphenyl was used as internal standard).

3. Results and discussion

3.1 Results of the catalyst characterization

The typical TG (Fig. 1) and XRD (Fig. 2) patterns demonstrated the formation of layered double hydroxides (LDHs). All the hydrotalcites showed three similar stages of weight loss in the TG curves. For HTZn_1.1Mg_2.0Al, the first step, ranging from 50 °C to 180 °C, is due to the evaporation of surface water on the sample. In the following stage, interlayer water molecules are lost up to 381 °C. Dehydroxylation or removal of the hydroxyl groups from the layers as water vapour and decomposition of the interlayer anions occur at higher temperatures up to 600 °C. As shown in Fig. 2, HTMg_3.0Al and HTZn_3.2Al showed the typical XRD patterns of the hydrotalcite structure with intense, sharp and symmetric peaks.³⁷ When the Zn component was introduced to HTMg_3.0Al to produce HTZn_1.1Mg_2.0Al, the diffraction peaks were still consistent with HTs, demonstrating that the layered structure was maintained. However, the layered structure was destroyed in HTZn_1.1Mg_2.0Al and ZnO diffraction peaks were observed after calcination. The composite oxides showed high specific surface areas (>100 m² g⁻¹) owing to their significant porosity (Table 1). All the oxides were mesoporous material with average pore sizes ranging from about 9 to 19 nm. Moreover, the sheet-like structure was also visualized from the SEM images (Fig. 3A), which exhibited mainly nanoplate-shaped crystals. After calcination at 400 °C (Fig. 3B), the visible nanoplate-like features were still present, suggesting that 400 °C was an appropriate treatment temperature in order to completely decompose the interlayer anions without phase segregation and sintering.¹³

Fig. 1 TGA curve of the hydrotalcite-like compounds.

Fig. 2 XRD patterns of (a) HTZn_3.2Al; (b) HTZn_1.1Mg_2.0Al; (c) HTMg_3.0Al; (d) Zn_1.1Mg_2.0AlO_4.6 and (e) Zn_1.1Mg_2.0AlO_4.6-reused (■: HTs; ▼: ZnO; ★: Zn(NH₃)₂(NCO)₂).

Table 1 Physical and base properties of the composite oxides derived from HTs

Catalyst	SBET (m^2 g^−1)	Dp (nm)	Vp (cm^3 g^−1)	Basic sites^a (μmol g^−1)
				Weak <100 °C	Medium 100–300 °C	Strong >300 °C	Total
a Determined by TPD.
Mg3.0AlO4.5	158	9	0.4	60	52	15	127
Zn3.2AlO4.7	103	19	0.5	15	—	—	15
Zn1.1Mg2.0AlO4.6	155	12	0.6	31	21	—	52
Zn1.1Mg2.0AlO4.6-reused	—	—	—	35	10	—	45

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Fig. 3 SEM images of (A) HTZn_1.1Mg_2.0Al and (B) Zn_1.1Mg_2.0AlO_4.6.

The basic surface properties of the composite oxide catalysts were studied by CO₂-TPD (Fig. 4) and assigned according to the temperature at which the peaks appeared (Table 1). The weakly basic sites of CO₂ desorption appeared at about 75 °C and were observed in all the catalysts. For Mg_3.0AlO_4.5, the peak for CO₂ desorbed from medium strength basic sites at 120 °C was attributed to metal–oxygen pairs such as Mg–O, Zn–O and Al–O. CO₂ desorption peaks at 120 °C were not observed for the Zn_3.2AlO_4.7 catalyst. The CO₂-TPD profile of a reused catalyst, denoted as Zn_1.1Mg_2.0AlO_4.6-reused, had more weakly basic sites, whereas the number of medium strength basic sites decreased. Moreover, it should be mentioned that among all the catalysts, Mg_3.0AlO_4.5 showed the highest desorption temperature of the strongly basic sites at about 400 °C, which was attributed to its unsaturated oxygen atoms.

Fig. 4 The CO₂-TPD profiles of (a) Mg_3.0AlO_4.5 (b) Zn_3.2AlO_4.7 (c) Mg_1.1Zn_2.0AlO_4.6 (d) Zn_1.1Mg_2.0AlO_4.6-reused.

3.2 2-Oxazolidinone syntheses from urea and epoxides

In our initial study, the reaction of urea and propylene oxide (PO) was chosen as the model reaction to explore the catalyst system (Table 2). In general, the reaction was carried out at 140 °C for 4 h in the presence of different catalysts. In the blank test (entry 1), the yield of 5-methyl-2-oxazolidinone was only 35%, which indicated that the catalyst was essential for the reaction to proceed successfully. Yields of 5-methyl-2-oxazolidinone were increased to 50%, 57% and 70% with ZnO, Al₂O₃ and MgO catalysts, respectively (entries 2–4). The main by-products with these catalysts were 1-amino-2-propanol and hydroxyl functionalized 2-oxazolidinone, as determined by GC-MS analysis. As shown in Scheme 2, 1-amino-2-propanol was formed by the side reaction between NH₃ and PO, which could also react with urea to form 5-methyl-2-oxazolidinone. When the 5-methyl-2-oxazolidinone concentration was relatively high, further ring opening of the epoxide occurred to generate hydroxyl functionalized 2-oxazolidinone. Moreover, a trace amount of 4-methyl-2-oxazolidinone was also detected due to the nucleophilic ring opening of PO at the methyl-substituted site. The composite oxides derived from thermal decomposition of hydrotalcites were also used as catalysts for the model reaction (entries 5–7). The ternary composite oxide Zn_1.1Mg_2.0AlO_4.6 displayed the highest catalytic activity with 82% yield of 5-methyl-2-oxazolidinone. Previous reports³⁸ illustrated that the reaction occurred via nucleophilic ring opening of PO at the less substituted site under basic conditions, followed by intramolecular cyclization to produce the product, 5-methyl-2-oxazolidinone. It can be conjectured that the yield of 5-methyl-2-oxazolidinone was mainly affected by the strength of the basic sites. Previously, the present authors measured the basic properties of the present oxide catalysts by temperature programmed desorption (TPD) of adsorbed CO₂ (Table 1). It was shown that Zn_3.2AlO_4.7 only has weakly basic sites, whereas Mg_3.0AlO_4.5 has strongly basic sites. The lower activity of Zn_3.2AlO_4.7 might therefore be due to its weak basicity (Table 1), which was unfavorable for the nucleophilic ring opening of PO, whereas Mg_3.0AlO_4.5 with its larger number of medium basic sites showed relatively lower catalytic activity, which was considered to be related to the presence of strong basic sites, promoting the by-product formation. Therefore, incorporation of a zinc component into Mg–Al oxides remarkably affected both the degree of basicity and the number of basic sites. Based on the preliminary results, it was concluded that the high activity and selectivity of Zn_1.1Mg_2.0AlO_4.6 for 5-methyl-2-oxazolidinone synthesis resulted from its basic properties. However, the catalyst morphology had little effect on the catalytic performance.

Table 2 Synthesis of 5-methyl-2-oxazolidinone from PO and urea with different catalysts and reaction conditions^a

Entry	Catalyst	T (°C)	t (h)	Yield^b (%)
a Reaction conditions: 10 mmol PO; 20 mmol urea; 0.05 g catalysts; 120–150 °C; 2–8 h.b Determined by gas chromatography.
1	—	140	4	35	3	15
2	ZnO	140	4	50	14	16
3	Al2O3	140	4	57	9	11
4	MgO	140	4	70	3	10
5	Zn3.2AlO4.7	140	4	65	6	10
6	Mg3.0AlO4.5	140	4	75	7	11
7	Zn1.1Mg2.0AlO4.6	140	4	82	2	5
8	Zn1.1Mg2.0AlO4.6	120	4	7	2	1
9	Zn1.1Mg2.0AlO4.6	130	4	56	5	16
10	Zn1.1Mg2.0AlO4.6	150	4	45	14	41
11	Zn1.1Mg2.0AlO4.6	140	2	65	15	2
12	Zn1.1Mg2.0AlO4.6	140	8	82	1	6
13	Zn1.1Mg2.0AlO4.6^1st	140	4	81	3	5
14	Zn1.1Mg2.0AlO4.6^2nd	140	4	81	3	6
15	Zn1.1Mg2.0AlO4.6^3rd	140	4	80	4	6

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Scheme 2 Possible reaction pathways for the reaction of urea and PO.

Subsequently, the impact of the reaction temperature was investigated (entries 8–10). The yield of 5-methyl-2-oxazolidinone sharply increased in the temperature range of 120–140 °C and decreased slightly when the reaction temperature exceeded 140 °C, probably due to promotion of the side reactions between PO and NH₃ or (5-methyl-2-oxazolidinone), which lead to the selectivity of 1-amino-2-propanol and hydroxyl functionalized 2-oxazolidinone increased. Thus, the optimal temperature was 140 °C. Finally, the impact of the reaction time on 5-methyl-2-oxazolidinone synthesis was investigated (entries 11–12). The yield of 5-methyl-2-oxazolidinone reached 82% after 4 h. Further prolonging the reaction time had no remarkable effect on increasing the yield of 5-methyl-2-oxazolidinone. Apart from the catalytic activity, the reusability of catalyst is another important issue. The results (entries 13–15) indicated that the yield of 5-methyl-2-oxazolidinone slightly decreased to 80% after 3 cycles. This may be due to catalyst leaching (about 36% wt Mg, 11% wt Zn and <0.1% wt Al were leached after 3 recycles), decline of the medium strength basic sites (Table 1) and phase transformations of ZnO during the reaction (a new phase of Zn(NH₃)₂(NCO)₂ was observed in spent catalysts by XRD, Fig. 2e).

3.3 Scope of the catalysts

To investigate the limitation and scope of this protocol, the reaction was tested using several different epoxides and urea to form corresponding 2-oxazolidinones under the optimized conditions, and the results are given in Table 3. Greater than 90% conversion and >80% selectivity for the desired 2-oxazolidinones were obtained with terminal epoxides (entries 1–6). The reaction of styrene oxide and urea at 140 °C produced merely 55% selectivity for the intended 5-substituted 2-oxazolidinone product, with a substantial quantity of the 4-substituted 2-oxazolidinone (45%) also being formed (entry 7). The low selectivity of the 5-substituted-2-oxazolidinones for the styrene oxide (entry 7) might be attributed to the conjugative effect derived from the aromatic ring, which would make attack at the phenyl substituted carbon more favorable, affording 4-substituted-2-oxazolidinones.³⁹ When cyclohexene oxide, an example of a disubstituted epoxide (entry 8), was used as the substrate, 80% conversion and 64% selectivity for the corresponding 2-oxazolidinone were obtained. The comparatively lower activity versus the other epoxides might be due to high steric hindrance of cyclohexene oxide. From the preliminary results, it can be conjectured that the basic Zn_0.8Mg_1.9AlO_4.2 catalyst has good catalytic performance for synthesis of various 5-substituted-2-oxazolidinones by epoxide opening reaction with urea.

Table 3 Synthesis of 2-oxazolidinones from various epoxides and urea^a

Entry	Epoxide	Major product	Conv. (%)	Sel.^b (%)
a Reaction conditions: 10 mmol epoxides; 20 mmol urea; 0.05 g Zn1.1Mg2.0AlO4.6; 140 °C; 8 h. Conversion and selectivity were determined by gas chromatography.b Selectivity of the 5-substituted-2-oxazolidinone.
1			99	89
2			99	81
3			99	88
4			92	80
5			94	87
6			96	88
7			99	55
8			80	64

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4. Conclusions

Production of value-added chemicals using urea as an active form of carbon dioxide is favorable for the sustainable development of the chemical industry. In this study, various 2-oxazolidinones were successfully synthesized from urea and epoxides in the absence of any solvent. This efficient and green protocol has the advantages of environmental friendliness, high yields and operational simplicity.

Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 21173240).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra21809a

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