Synthesis of imidazolidin-2-ones employing dialkyl carbonates as an ecofriendly carbonylation source

Abstract

A new approach to the synthesis of imidazolidin-2-ones by carbonylation of vicinal diamines with dialkyl carbonates using Pb(NO₃)₂ and Cu(II) salts as catalysts has been described in the present protocol. A comparative study using Cu(II) salts and Pb(NO₃)₂ as catalysts has suggested Cu(NO₃)₂ and CuCl₂·2H₂O salts to be as promising as Pb(NO₃)₂ and can replace the latter in the carbonylation reactions employing dialkyl carbonates.

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Introduction

Imidazolidines are biologically active pharmacophores¹ and important synthetic intermediates² in medicinal chemistry. In addition, they are precursors of both cyclic guanidines³ and N-heterocyclic carbine (NHC) ligands in coordination chemistry and homogeneous catalysis.⁴ They have attracted attention because of their wide range of physiological activities like antidiabetic,⁵ anticonvulsant,⁶ antitumor,⁷ antiarrhythmic,⁸ anti-parasitic and anti-microbial.⁹ They are also helpful in the treatment of Chagas disease.¹⁰ Imidazolidine moieties with potential bioactivity are featured in a large number of natural products like Mezlocillin (I), biotin (II) and mauritamide A (III) etc (Fig. 1).

Fig. 1 Natural products with imidazolidine moiety.

Classical method of synthesis involves carbonylation of variously substituted amines with phosgene.¹¹ The use of an alternative to toxic phosgene in the carbonylation process has been a keen area under research.¹² In search of an alternative to toxic phosgene, many non-phosgene routes including reductive carbonylation¹³ and oxidative carbonylation¹⁴ by using CO as a source, and the use of transition metal as catalysts,¹⁵ have been extensively studied. Although the desired products are obtained in good yields via these routes but the major drawback of these methods is use of poisonous CO and in others, use of larger amount of dehydrating agents, appropriate bases, expensive alkyl chlorides and tedious work-up, leading to the generation of large amount of toxic waste. Carbonylation employing CO₂ as an alternative to phosgene has also been reported,¹⁶ but this route was more expensive as well as less environment friendly. In the last two decades, use of dimethyl carbonate along with Mn, Zr, Zn and Pb compounds as catalysts,¹⁷ has received much pace in the synthesis of isocyanates and carbamates because of their eco-friendly nature and non-toxicity.¹⁸ However, the later methods do employ pressure vessel (autoclave) conditions. Only one paper by Xiao et al.¹⁹ reports the synthesis of 2-imidazolidinones employing cyclic carbonates. But the later method do suffers from one or more drawbacks like low yields, use of external solvent, longer reaction time (5–6 h) and in sense it is limited to aliphatic substrates only. So in order to overcome these difficulties, it is still desirable to search for a simple and efficient synthetic method for the synthesis of imdazolidin-2-ones. To the best of our knowledge, the synthesis of imidazolidines by the carbonylation of vicinal diamines with dialkyl carbonates has not been investigated so far. So, here, we report the synthesis of a number of imidazolidin-2-one derivatives by the carbonylation of various synthesized vicinal diamines with dialkyl carbonates in presence of Pb(NO₃)₂ and Cu(II) salts as catalyst. Pb(NO₃)₂ was chosen as the catalyst as it gives best results in terms of yields among various compounds of Zn, Zr, Mn or Pb used as catalysts in a variety of carbonylation reactions.¹⁷ Further the same reaction has also been carried out using Cu(II) salts in place of Pb(NO₃)₂ and the results obtained in our studies suggested Cu(II) salts as promising catalysts for cabonylation reactions with dialkyl carbonates in place of hazardous Pb(II) salts. In this protocol, reaction has been performed in two-necked RBF under inert nitrogen atmosphere placed in an oil bath heated at the reaction temperature. So, the need for pressure vessel has been compensated. So, this protocol has the advantageous features of mild reaction conditions, simple experimental procedure, high yields, low time requirement, avoidance of volatile organic solvents and toxic phosgene.

Results and discussion

Synthesis of vicinal diamine substrates

For the purpose of our studies, substrates vicinal diamines were synthesized by the reduction of α-aminonitriles. Initially, α-aminonitriles were obtained in good to excellent yields by the treatment of benzaldehyde, amine with Zn(CN)₂ in EtOH–AcOH (3 : 1) as per our method reported in literature.²⁰ For this purpose, a mixture of amine–aldehyde–zinc cyanide in the ratio 1 : 1 : 1 in ethanol–acetic acid (3 : 1) as solvent was stirred at room temperature for 20–30 minutes (Scheme 1). The physical data (mp, IR, NMR) of known compounds were found to be identical with those reported in the literature.²⁰

Scheme 1 Sequential reactions for synthesis of α-aminonitriles, followed by reduction employing LiAlH₄.

The various synthesized α-aminonitriles were subjected to reduction using LiAlH₄ in dry THF. For this purpose initially 1a was treated with 1 equiv. LiAlH₄ in dried THF as the solvent. In an effort to optimize the reaction conditions, 1a was taken as a reference compound and the quantities of LiAlH₄ were varied, and the results are summarized in Table 1.

Table 1 Optimization of reaction conditions for reduction of α-aminonitrile (1a) using LiAlH₄^a

Entry	LiAlH4 equiv. per equiv. of 1a	Duration (min)	% Conversion^b of 1a
a 1a (5 mmol), THF (10 mL).b Determined by GC.
1	0.8	30	58
2	0.8	45	74
3	0.8	60	81
4	1.0	30	62
5	1.0	45	77
6	1.0	60	89
7	1.2	30	63
8	1.2	45	78
9	1.2	60	100
10	1.5	30	64
11	1.5	45	81
12	1.5	60	100

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Complete reduction was observed using 1.2 equiv. of LiAlH₄ corresponding to 1 equiv. of the reactant in 60 minutes duration (Table 1, entry 9). A further increase in these quantities did not have the desired result. After reaction conditions were optimized, the various substrates 1a–k, were subjected to reduction under the optimized reaction conditions. The work up and purification of the reaction mixture in each case afforded a mixture of α-(aminomethyl)-N-substituted vicinal diamine and N-substituted monoamine (Table 2). The two products were characterized by their IR, ¹H-NMR, ¹³C-NMR and HRMS analysis. The first product arises through normal reduction of nitrile functional group of α-amino nitriles, while the second product arises through the nucleophilic displacement of nitrile functional group with hydride ion of lithium aluminium hydride. The latter is called reductive decyanation (Table 2).²¹

Table 2 LiAlH₄ affected reduction of α-aminonitriles^a

Entry	R^1	R^2	2 (% Yield^b)	3 (% Yield^b)
a 1 (5 mmol), LiAlH4 (6 mmol) and THF (10 mL).b On basis of isolated yields.
1	Ph	Ph	36	48
2	2-CH3C6H4	Ph	31	60
3	3-CH3C6H4	Ph	35	52
4	4-CH3C6H4	Ph	29	51
5	2-ClC6H4	Ph	27	57
6	3-ClC6H4	Ph	24	58
7	4-ClC6H4	Ph	26	59
8	2-Furanyl	Ph	29	56
9	2-Thiophenyl	Ph	31	51
10	Ph	Et	38	52
11	Ph	C6H11	33	48

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Carbonylation of vicinal diamines with dialkyl carbonates

For the synthesis of titled compounds (imidazolidin-2-ones), the carbonylation of vicinal diamine 2a (5 mmol), obtained as one of the product of the reduction of α-aminonitriles, was performed with dimethyl and diethyl carbonates 4 (30 mmol) at 453 K for 1 h without using any external solvent and catalyst. Without a catalyst, the product imidazolidin-2-one (5a) was obtained in 33% and 31% yield respectively with dimethyl and diethyl carbonate (Scheme 2) along with unreacted 2a (45% in each case). No other side product was detected by TLC analysis.

Scheme 2 Carbonylation of reduced compound 2a with dialkyl carbonates 4.

In an effort to improve the yield, the same reaction was carried out using varied quantities of Pb(NO₃)₂ and Cu(II) salts as catalysts, and the results are summarised in Table 3.

Table 3 Optimisation of reaction conditions for carbonylation reaction of 2a with dialkyl carbonates

Entry	Catalyst	mol%	Temp. [K]	Time [h]	Yield^a [%]	Yield^b [%]
a Isolated yield, reaction conditions: 2a (5 mmol), 4 = DMC (30 mmol).b Isolated yield, reaction conditions: 2a (5 mmol), 4 = DEC (30 mmol).c Yields shown in parentheses are calculated on the basis of recovered starting amine.
1	Pb(NO3)2	20	453	1	64 (80)^c	59 (71)
2		10	453	1	62 (77)	49 (65)
3		5	453	1	47 (61)	37 (52)
4	CuCl2·2H2O	20	453	1	65 (79)	58 (71)
5		10	453	1	59 (74)	50 (65)
6		5	453	1	43 (57)	41 (52)
7	Cu(NO3)2	20	453	1	65 (81)	55 (72)
8		10	453	1	63 (78)	55 (69)
9		10	443	1	52 (67)	47 (60)
10		10	463	1	67 (82)	59 (74)
11		10	453	0.8	57 (73)	46 (64)
12		10	453	1.2	66 (80)	56 (72)
13		10	453	1.5	63 (77)	53 (67)
14		5	453	1	48 (60)	42 (58)
15	Cu(OAc)2	20	453	1	45 (58)	41 (53)
16		10	453	1	34 (45)	29 (40)
17		5	453	1	29 (41)	26 (37)
18	CuCO3	20	453	1	46 (55)	38 (52)
19		10	453	1	32 (42)	30 (38)
20		5	453	1	24 (38)	21 (33)
21	No catalyst	—	453	1	20 (33)	17 (31)

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It was found that yields obtained with CuCl₂·2H₂O and Cu(NO₃)₂ were as good as Pb(NO₃)₂. Further, Pb(NO₃)₂, CuCl₂·2H₂O and Cu(NO₃)₂ showed similar activity at 20 mol% and 10 mol%, but lowering the amount of catalyst to 5 mol% led to lower yields. Cu(OAc)₂ and CuCO₃ were only effective at 20 mol% concentration. It was also observed that under identical conditions; slightly higher yields were obtained with dimethyl carbonate in comparison to diethyl carbonate probably due to more solubility of catalyst into the former. High selectivity was also observed in these reactions as product formed was exclusively imidazolidin-2-one without isolation of any N-methylated by-product as reported in other carbonylation reactions employing dimethyl carbonate.^17e Cu(NO₃)₂ gave best results among Cu(II) salts (Table 3, entries 7 and 8). So 10 mol% Cu(NO₃)₂ was used as a probe to evaluate the effect of temperature and reaction time on the yields of 5a. It was found that, raising the reaction temperature from 443 K to 453 K improved the yield of 5a to 81% (Table 3, entry 7) and a further increase in temperature didn't show the desired results (Table 3, entry 10). Maximum yield of 5a was obtained in 1 h duration (Table 3, entry 7), but a longer reaction time did not improve the yields further (Table 3, entries 12 and 13).

Under the optimised reaction conditions, the differently substituted vicinal diamine substrates 2a–k were subjected to carbonylation reaction to afford the respective products in good yields (Table 4). The resulted imidazolidin-2-one derivatives 5a–k were characterized by ¹H-NMR, ¹H-NMR-COSY, ¹³C-NMR, I.R. and Mass spectra results (HRMS). Further to check the viability of the presented protocol, aliphatic amines too were subjected to carbonylation reactions under the similar conditions and results were found to be as good as in case of aromatic amines (Table 4, entries 10 and 11).

Table 4 Synthesis of imidazolidin-2-ones by carbonylation of 2a–k with dialkyl carbonates using Cu(NO₃)₂^a

Entry	R^1	R^2	Yield^b [%]	Yield^c [%]
a 2 (5 mmol), 4 (30 mmol) and Cu(NO3)2 (10 mol%), 453 K, 1 h.b yield on basis of recovered starting amine 4 = DMC.c Isolated yield, 4 = DEC.
1	Ph	Ph	81 (5a)	71 (5a)
2	2-CH3C6H4	Ph	83 (5b)	75 (5b)
3	3-CH3C6H4	Ph	68 (5c)	60 (5c)
4	4-CH3C6H4	Ph	77 (5d)	71 (5d)
5	2-ClC6H4	Ph	63 (5e)	56 (5e)
6	3-ClC6H4	Ph	71 (5f)	66 (5f)
7	4-ClC6H4	Ph	76 (5g)	69 (5g)
8	2-Furanyl	Ph	68 (5h)	63 (5h)
9	2-Thiophenyl	Ph	64 (5i)	57 (5i)
10	Ph	Et	84 (5j)	79 (5j)
11	Ph	C6H11	78 (5k)	70 (5k)

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Reaction mechanism

As far as the role of catalyst is concerned, Cu(II) species seems to serve as a Lewis acid that enhances the polarisation of carbonyl group of dialkyl carbonate thereby increases the chances of attack by the amine functionality and the plausible reaction mechanism is as shown in Fig. 2.^17e

Fig. 2 Plausible mechanism of carbonylation of vicinal diamine employing Cu(II) salts.

Conclusion

In summary, we have successfully presented a new route for the synthesis of imidazolidines by the carbonylation of vicinal diamines with dialkyl carbonates as a substitute for toxic phosgene under Pb(NO₃)₂ and Cu(II) salts catalytic conditions, without the use of any harsh reaction conditions and volatile organic solvents. Cu(II) salts have been used for the first time for such carbonylation reactions and Cu(NO₃)₂ and CuCl₂·2H₂O has provided results as much promising as that in case of Pb(NO₃)₂ and can replace the latter in various carbonylation reactions employing dialkyl carbonates. Since Pb and its compounds are much hazardous, so their replacement by Cu(II) salts serves as a step towards green chemistry.

Experimental

General

¹H NMR spectra were recorded on BRUKER 400 MHz spectrometer in CDCl₃ solution and the chemical shifts are reported in parts per million (δ) relative to internal standard TMS (0 ppm). The coupling constants (J) are reported in Hertz (Hz). ¹³C NMR spectra were obtained at 100 MHz and referenced to the internal solvent signals (central peak is 77.00 CDCl₃). Mass spectra were recorded on Thermo Scientific, LTQ-XL LCMS. HRMS data of unknown compounds was recorded on maXis™ Mass Spectrometer. IR spectra were recorded on a Perkin Elmer RX I FTIR Spectrophotometer. The gas chromatograph were recorded on GC-MS QP-2010 plus with RTX-1MS (30 m × 0.25 mm ID × 0.25 μm) capillary column. THF was dried over Na wire in the presence of benzophenone and distilled under an argon atmosphere. The freshly distilled THF was used for all reactions. DMC and DEC were dehydrated using molecular sieves 4 Å. Pb(NO₃)₂ and Cu(II) salts were dried under vacuum at 393 K for 1 h prior to use. All reactions were carried out under an inert nitrogen atmosphere in oven-dried glassware. Purification of compounds was done with column chromatography over silica gel using hexane–ethyl acetate mixture as eluent.

General procedure for synthesis of α-aminonitriles

A mixture of amine (5 mmol), aldehyde (5 mmol), zinc cyanide (5 mmol) and ethanol–acetic acid (3 : 1) was stirred at ambient temperature for the appropriate time (20–50 minutes). After completion of the reaction as indicated by TLC, the crude product was purified by recrystallization from diethyl ether (solid products) or by column chromatography using silica gel and mixtures of hexane–ethyl acetate of increasing polarity. The physical data (mp, IR, NMR) of known compounds were found to be identical with those reported in the literature.²⁰

General procedure for reduction of α-aminonitriles

Into a flame dried two-necked round bottomed flask, equipped with a magnetic stirrer bar, septum cap and a bubbler, was taken LiAlH₄ (228 mg, 6 mmol, 1.2 equiv). It was cooled to 0–5 °C by placing it in an ice bath. To which dried THF (5 mL) was added drop wise followed by drop wise addition of solution of α-aminonitrile (1.04 g, 5 mmol, 1 equiv.) in dried THF (5 mL) under an inert nitrogen atmosphere with continuous stirring using magnetic stirrer. After complete addition the ice bath was removed and the mixture was further stirred at r.t. using magnetic stirrer for 1 hour. The reaction mixture was cooled again, the excess LiAlH₄ was quenched using ethyl acetate and water. The ethyl acetate layer was separated, dried with anhydrous Na₂SO₄ and concentrated on a rotary evaporator. After evaporation of the solvent, the residue was subjected to column chromatography (silica gel) using hexane–ethyl acetate mixture as eluent to obtain reduced products 2 and 3.

N-(2-Amino-1-phenylethyl)benzenamine (2a). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.21; IR (ν cm⁻¹, CHCl₃): 3363, 3406 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.59–3.62 (m, 2H), 4.46 (dd, J = 5.3, 6.9 Hz, 1H), 4.94 (s, 1H, NH), 5.71 (s, 2H, NH₂), 6.49–6.66 (m, 3H), 7.05–7.27 (m, 7H); ¹³C NMR (100 MHz, CDCl₃): δ 44.75, 59.03, 113.36, 117.66, 126.54, 127.78, 128.96, 129.18, 140.56, 146.98; MS: m/z: 212 [M]⁺; HRMS (ESI) calcd for C₁₄H₁₆N₂ [M + H]⁺ 213.1307, found [M + H]⁺ 213.1311.

N-Benzylbenzenamine (3a). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.89; IR (ν cm⁻¹, CHCl₃): 3380 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 4.09 (s, 1H, NH), 4.32 (s, 2H), 6.62–6.73 (m, 3H), 7.15–7.39 (m, 7H); ¹³C NMR (100 MHz, CDCl₃): δ 48.37, 112.91, 117.64, 127.28, 127.56, 128.67, 129.30, 139.38, 148.08; MS: m/z: 183 [M]⁺; HRMS (ESI) calcd for C₁₃H₁₃N [M + H]⁺ 184.1042, found [M + H]⁺ 184.1047.

N-(2-Amino-1-o-tolylethyl)benzenamine (2b). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.20; IR (ν cm⁻¹, CHCl₃): 3364, 3408 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.00 (s, 3H, CH₃), 3.56–3.64 (m, 2H), 4.45 (dd, J = 6.0, 6.2 Hz, 1H), 4.98 (s, 1H, NH), 5.81 (s, 2H, NH₂), 6.52–6.68 (m, 3H), 7.05–7.38 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 18.98, 48.34, 60.43, 112.74, 117.52, 126.15, 127.65, 127.83, 128.95, 129.20, 133.71, 139.46, 148.18; MS: m/z: 226 [M]⁺; HRMS (ESI) calcd for C₁₅H₁₈N₂ [M + H]⁺ 227.1469, found [M + H]⁺ 227.1467.

N-(2-Methylbenzyl)benzenamine (3b). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.92; IR (ν cm⁻¹, CHCl₃): 3384 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.34 (s, 3H, CH₃), 3.84 (s, 1H, NH), 4.23 (s, 2H), 6.59–6.72 (m, 3H), 7.12–7.46 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.00, 44.78, 113.16, 117.59, 125.57, 125.76, 126.95, 128.14, 129.21, 129.33, 140.68, 147.11; MS: m/z: 197 [M]⁺; HRMS (ESI) calcd for C₁₄H₁₅N [M + H]⁺ 198.1204, found [M + H]⁺ 198.1205.

N-(2-Amino-1-m-tolylethyl)benzenamine (2c). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.24; IR (ν cm⁻¹, CHCl₃): 3363, 3410 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.21 (s, 3H, CH₃), 3.54–3.64 (m, 2H), 4.49 (dd, J = 5.1, 6.4 Hz, 1H), 4.98 (s, 1H, NH), 6.03 (s, 2H, NH₂), 6.56–6.67 (m, 3H), 7.02–7.34 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.28, 45.61, 57.21, 113.45, 117.83, 126.29, 127.62, 128.00, 128.41, 129.07, 129.54, 141.60, 146.42; MS: m/z: 226 [M]⁺; HRMS (ESI) calcd for C₁₅H₁₈N₂ [M + H]⁺ 227.1469, found [M + H]⁺ 227.1464.

N-(3-Methylbenzyl)benzenamine (3c). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.91; IR (ν cm⁻¹, CHCl₃): 3382 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.33 (s, 3H, CH₃), 4.06 (s, 1H, NH), 4.30 (s, 2H), 6.69–6.82 (m, 3H), 7.17–7.40 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 21.09, 46.42, 112.74, 117.52, 126.20, 127.47, 128.30, 129.20, 129.32, 130.44, 136.39, 148.28; MS: m/z: 197 [M]⁺; HRMS (ESI) calcd for C₁₄H₁₅N [M + H]⁺ 198.1204, found [M + H]⁺ 198.1201.

N-(2-Amino-1-p-tolylethyl)benzenamine (2d). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.22; IR (ν cm⁻¹, CHCl₃): 3361, 3407 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.04 (s, 3H, CH₃), 3.56–3.63 (m, 2H), 4.51 (dd, J = 5.4, 6.9 Hz, 1H), 4.93 (s, 1H, NH), 5.98 (s, 2H, NH₂), 6.56–6.67 (m, 3H), 7.12–7.34 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.21, 43.32, 56.44, 114.06, 117.22, 126.96, 127.19, 128.11, 129.23, 138.16, 148.90; MS: m/z: 226 [M]⁺; HRMS (ESI) calcd for C₁₅H₁₈N₂ [M + H]⁺ 227.1469, found [M + H]⁺ 227.1465.

N-(4-Methylbenzyl)benzenamine (3d). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.88; IR (ν cm⁻¹, CHCl₃): 3384 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 2.28 (s, 3H, CH₃), 3.96 (s, 1H, NH), 4.24 (s, 2H), 6.67–6.78 (m, 3H), 7.07–7.34 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 29.72, 44.75, 113.16, 117.73, 126.45, 127.69, 128.94, 129.13, 140.12, 147.18; MS: m/z: 197 [M]⁺; HRMS (ESI) calcd for C₁₄H₁₅N [M + H]⁺ 198.1204, found [M + H]⁺ 198.1209.

N-(2-Amino-1-(2-chlorophenyl)ethyl)benzenamine (2e). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.23; IR (ν cm⁻¹, CHCl₃): 3360, 3396 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.52–3.59 (m, 2H), 4.57 (dd, J = 4.1, 8.1 Hz, 1H), 5.00 (s, 1H, NH), 5.69 (s, 2H, NH₂), 6.43–6.64 (m, 3H), 7.03–7.39 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 48.19, 62.33, 113.72, 117.22, 126.96, 127.69, 128.13, 129.30, 129.62, 133.10, 137.80, 147.18; MS: m/z: 246 [M]⁺, 248 [M + 2]⁺; HRMS (ESI) calcd for C₁₄H₁₅N₂Cl [M + H]⁺ 247.0918, found [M + H]⁺ 247.0923.

N-(2-Chlorobenzyl)benzenamine (3e). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.88; IR (ν cm⁻¹, CHCl₃): 3382 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 4.01 (s, 1H, NH), 4.31 (s, 2H), 6.61–6.72 (m, 3H), 7.14–7.37 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 46.60, 113.00, 117.72, 126.72, 127.69, 128.48, 129.58, 130.70, 136.55, 137.37, 148.62; MS: m/z: 217 [M]⁺, 219 [M + 2]⁺; HRMS (ESI) calcd for C₁₃H₁₂NCl [M + H]⁺ 218.0658, found [M + H]⁺ 218.0652.

N-(2-Amino-1-(3-chlorophenyl)ethyl)benzenamine (2f). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.24; IR (ν cm⁻¹, CHCl₃): 3360, 3398 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.52–3.60 (m, 2H), 4.56 (dd, J = 4.2, 8.0 Hz, 1H), 5.03 (s, 1H, NH), 5.70 (s, 2H, NH₂), 6.66–6.76 (m, 3H), 6.93–7.24 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 44.17, 57.45, 113.73, 117.91, 125.65, 126.97, 127.33, 128.52, 129.13, 129.75, 138.18, 148.77; MS: m/z: 246 [M]⁺, 248 [M + 2]⁺; HRMS (ESI) calcd for C₁₄H₁₅N₂Cl [M + H]⁺ 247.0918, found [M + H]⁺ 247.0920.

N-(3-Chlorobenzyl)benzenamine (3f). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.89; IR (ν cm⁻¹, CHCl₃): 3380 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 4.02 (s, 1H, NH), 4.29 (s, 2H), 6.62–6.79 (m, 3H), 7.14–7.33 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 48.19, 113.02, 117.63, 127.71, 128.45, 129.35, 129.46, 129.51, 129.91, 137.07, 148.42; MS: m/z: 217 [M]⁺, 219 [M + 2]⁺; HRMS (ESI) calcd for C₁₃H₁₂NCl [M + H]⁺ 218.0658, found [M + H]⁺ 218.0655.

N-(2-Amino-1-(4-chlorophenyl)ethyl)benzenamine (2g). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.23; IR (ν cm⁻¹, CHCl₃): 3361, 3402 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.56–3.63 (m, 2H), 4.59 (dd, J = 5.1, 6.7 Hz, 1H), 4.99 (s, 1H, NH), 5.68 (s, 2H, NH₂), 6.66–6.79 (m, 3H), 7.02–7.29 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 46.73, 55.81, 113.13, 117.63, 126.25, 127.22, 128.02, 128.67, 139.21, 148.26; MS: m/z: 246 [M]⁺, 248 [M + 2]⁺; HRMS (ESI) calcd for C₁₄H₁₅N₂Cl [M + H]⁺ 247.0918, found [M + H]⁺ 247.0924.

N-(4-chlorobenzyl)benzenamine (3g). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.86; IR (ν cm⁻¹, CHCl₃): 3384 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.99 (s, 1H, NH), 4.31 (s, 2H), 6.61–6.78 (m, 3H), 6.93–7.30 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 48.34, 112.87, 117.59, 127.28, 127.56, 128.68, 129.32, 139.46, 148.18; MS: m/z: 217 [M]⁺, 219 [M + 2]⁺; HRMS (ESI) calcd for C₁₃H₁₂NCl [M + H]⁺ 218.0658, found [M + H]⁺ 218.0654.

N-(2-Amino-1-(furan-2-yl)ethyl)benzenamine (2h). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.20; IR (ν cm⁻¹, CHCl₃): 3358, 3408 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.55–3.63 (m, 2H), 4.44 (dd, J = 6.3, 7.2 Hz, 1H), 5.01 (s, 1H, NH), 6.04 (s, 2H, NH₂), 6.50–6.65 (m, 3H), 7.04–7.25 (m, 5H); ¹³C NMR (CDCl₃, 100 MHz): δ 48.29, 62.05, 112.92, 117.90, 127.55, 128.35, 129.32, 140.18, 146.67, 150.47; MS: m/z: 202 [M]⁺; HRMS (ESI) calcd for C₁₂H₁₄N₂O [M + H]⁺ 203.1106, found [M + H]⁺ 203.1109.

N-((Furan-2-yl)methyl)benzenamine (3h). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.90; IR (ν cm⁻¹, CHCl₃): 3384 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 4.03 (s, 1H, NH), 4.49 (s, 2H), 6.86–7.04 (m, 3H), 7.43–7.75 (m, 5H); ¹³C NMR (CDCl₃, 100 MHz): δ 48.33, 112.85, 117.58, 120.35, 128.66, 130.94, 143.39, 145.41, 151.13; MS: m/z: 173 [M]⁺; HRMS (ESI) calcd for C₁₁H₁₁NO [M + H]⁺ 174.0841, found [M + H]⁺ 174.0844.

N-(2-Amino-1-(thiophen-2-yl)ethyl)benzenamine (2i). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.23; IR (ν cm⁻¹, CHCl₃): 3360, 3404 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.35–3.40 (m, 2H), 4.37 (dd, J = 5.0, 6.5 Hz, 1H), 5.17 (s, 1H, NH), 5.71 (s, 2H, NH₂), 6.41–6.62 (m, 3H), 6.96–7.27 (m, 5H); ¹³C NMR (100 MHz, CDCl₃): δ 46.42, 58.63, 112.82, 117.50, 126.38, 127.47, 128.30, 129.32, 136.39, 148.28; MS: m/z: 218 [M]⁺; HRMS (ESI) calcd for C₁₂H₁₄N₂S [M + H]⁺ 219.0872, found [M + H]⁺ 219.0877.

N-((Thiophen-2-yl)methyl)benzenamine (3i). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.87; IR (ν cm⁻¹, CHCl₃): 3382 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 3.87 (s, 1H, NH), 4.18 (s, 2H), 6.45–6.68 (m, 3H), 6.96–7.20 (m, 5H); ¹³C NMR (100 MHz, CDCl₃): δ 48.04, 113.66, 117.61, 127.49, 128.79, 129.10, 136.28, 137.01, 148.13; MS: m/z: 189 [M]⁺; HRMS (ESI) calcd for C₁₁H₁₁NS [M + H]⁺ 190.0612, found [M + H]⁺ 190.0607.

N-Ethyl-1-phenylethane-1,2-diamine (2j). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.29; IR (ν cm⁻¹, CHCl₃): 3429, 3534 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 1.31 (t, J = 7.8 Hz, 3H), 2.39–2.42 (q, J = 7.6 Hz, 2H), 3.51–3.55 (m, 2H), 4.50 (dd, J = 5.7, 6.3 Hz, 1H), 5.06 (s, 1H, NH), 5.68 (s, 2H, NH₂), 6.82–6.98 (m, 3H), 7.09–7.18 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 18.38, 44.35, 52.27, 58.87, 128.66, 128.92, 129.32, 130.84, 135.44; MS: m/z: 164 [M]⁺; HRMS (ESI) calcd for C₁₀H₁₆N₂ [M + H]⁺ 165.1313, found [M + H]⁺ 165.1312.

N-Benzylethanamine (3j). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.88; IR (ν cm⁻¹, CHCl₃): 3429 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 1.23 (t, J = 8.1 Hz, 3H), 2.49–2.52 (q, J = 7.8 Hz, 2H), 3.86 (s, 1H, NH), 4.25 (s, 2H), 6.80–6.96 (m, 3H), 7.09–7.18 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 19.38, 43.67, 59.49, 128.84, 129.37, 130.10, 135.27; MS: m/z: 135 [M]⁺; HRMS (ESI) calcd for C₉H₁₃N [M + H]⁺ 136.1048, found [M + H]⁺ 136.1052.

N-(2-Amino-1-phenylethyl)cyclohexanamine (2k). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.22; IR (ν cm⁻¹, CHCl₃): 3427, 3521 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 0.83–1.08 (m, 3H), 1.11–1.29 (m, 4H), 1.65 (t, J = 1.4 Hz, 1H), 1.72 (d, J = 3.5 Hz, 3H), 3.52–3.63 (m, 2H), 4.42 (dd, J = 6.0, 6.4 Hz, 1H), 4.99 (s, 1H, NH), 5.73 (s, 2H, NH₂), 6.96–7.00 (m, 1H), 7.17–7.20 (m, 2H), 7.26–7.32 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.83, 25.56, 25.58, 28.59, 28.63, 52.74, 53.41, 59.42, 62.84, 129.67, 129.94, 131.68, 132.02, 135.66; MS: m/z: 218 [M]⁺; HRMS (ESI) calcd for C₁₄H₂₂N₂ [M + H]⁺ 219.1777, found [M + H]⁺ 219.1774.

N-Benzylcyclohexanamine (3k). Light yellow oil; R_f (20% CH₃COOEt/C₆H₁₄) 0.85; IR (ν cm⁻¹, CHCl₃): 3421 cm⁻¹ (N–H); ¹H NMR (400 MHz, CDCl₃): δ 0.93–1.08 (m, 3H), 1.11–1.29 (m, 4H), 1.64 (t, J = 1.4 Hz, 1H), 1.72 (d, J = 3.5 Hz, 3H), 3.91 (s, 1H, NH), 4.38 (s, 2H), 6.96–7.00 (m, 1H), 7.17–7.20 (m, 2H), 7.26–7.32 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 24.80, 28.56, 28.65, 52.76, 53.48, 60.03, 62.97, 129.66, 129.86, 131.38, 132.00, 135.82; MS: m/z: 189 [M]⁺; HRMS (ESI) calcd for C₁₃H₁₉N [M + H]⁺ 190.1512, found [M + H]⁺ 190.1517.

General procedure for catalytic carbonylation of vicinal diamines with dialkyl carbonates using Pb(NO₃)₂/Cu(II) salt as catalyst

Pb(NO₃)₂/Cu(II) salt was dried by heating under vacuum at 393 K for 1 h prior to use. Into a flame dried two-necked round-bottomed flask equipped with a magnetic stirrer bar, septum cap and a bubbler, was placed 5 mmol of vicinal diamine 2 and 30 mmol of freshly distilled dialkyl carbonate (dimethyl/diethyl carbonate) 4 under an inert atmosphere of nitrogen. 0.5 mmol of catalyst was charged into it and the RBF was set in an oil-bath heated at the reaction temperature 453 K for 1 hour. The reaction mixture was stirred with a magnetic stirrer during the reaction. After the commencement of reaction time, the contents were cooled to room temperature and the spent catalyst was filtered off. The filtrate was then evaporated to yield a pale yellow viscous liquid, which was subjected to column chromatography using hexane–ethyl acetate mixture as eluent to get the cyclized product imidazolidine-2-one 5. Further elution of the column with same solvent afforded the unreacted starting material 2. Similar procedure was followed with other variously substituted diamines. All the new compounds were characterized by ¹H NMR, ¹³C NMR, IR spectroscopy and mass spectrometry (HRMS).

1,5-Diphenylimidazolidin-2-one (5a). Brownish-yellow viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.63; IR (ν cm⁻¹, CHCl₃): 1700, 3382 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.52 (t, J = 6.4 Hz, 2H), 4.46 (t, J = 6.3 Hz, 1H), 4.87 (s, 1H, NH), 6.52–6.69 (m, 3H), 7.06–7.35 (m, 7H); ¹³C NMR (100 MHz, CDCl₃): δ 46.28, 59.66, 113.35, 117.47, 126.55, 127.65, 128.89, 129.14, 140.88, 147.11, 171.63; HRMS (ESI) calcd for C₁₅H₁₄N₂O [M + H]⁺ 239.1179, found [M + H]⁺ 239.1177.

1-Phenyl-5-o-tolylimidazolidin-2-one (5b). Brownish-yellow viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.65; IR (ν cm⁻¹, CHCl₃): 1702, 3384 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 2.42 (s, 3H), 3.63 (t, J = 6.5 Hz, 2H), 4.39 (t, J = 5.7 Hz, 1H), 4.84 (s, 1H, NH), 6.41–6.71 (m, 3H), 7.03–7.35 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.18, 43.05, 55.36, 113.08, 117.43, 125.70, 126.03, 127.23, 127.50, 128.93, 135.15, 139.33, 147.14, 171.20; HRMS (ESI) calcd for C₁₆H₁₆N₂O [M + H]⁺ 253.1335, found [M + H]⁺ 253.1339.

1-Phenyl-5-m-tolylimidazolidin-2-one (5c). Brownish-yellow viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.69; IR (ν cm⁻¹, CHCl₃): 1700, 3384 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 2.29 (s, 3H), 3.58 (t, J = 6.5 Hz, 2H), 4.42 (t, J = 6.4 Hz, 1H), 4.90 (s, 1H, NH), 6.55–6.70 (m, 3H), 7.07–7.36 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 21.04, 44.14, 58.63, 113.36, 117.55, 126.45, 127.13, 128.30, 129.51, 129.62, 138.41, 139.12, 143.70, 169.65; HRMS (ESI) calcd for C₁₆H₁₆N₂O [M + H]⁺ 253.1335, found [M + H]⁺ 253.1337.

1-Phenyl-5-p-tolylimidazolidin-2-one (5d). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.61; IR (ν cm⁻¹, CHCl₃): 1706, 3380 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 2.33 (s, 3H), 3.55 (t, J = 6.4 Hz, 2H), 4.44 (t, J = 6.8 Hz, 1H), 4.96 (s, 1H, NH), 6.59–6.73 (m, 3H), 7.04–7.34 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 19.32, 44.16, 55.78, 113.46, 117.24, 126.77, 127.71, 128.23, 136.33, 139.21, 142.70, 170.16; HRMS (ESI) calcd for C₁₆H₁₆N₂O [M + H]⁺ 253.1335, found [M + H]⁺ 253.1339.

5-(2-Chlorophenyl)-1-phenylimidazolidin-2-one (5e). Brownish-yellow viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.65; IR (ν cm⁻¹, CHCl₃): 1702, 3382 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.50 (t, J = 6.5 Hz, 2H), 4.57 (t, J = 6.4 Hz, 1H), 4.97 (s, 1H, NH), 6.64–6.76 (m, 3H), 7.05–7.37 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 45.19, 53.14, 112.67, 117.97, 126.62, 127.14, 127.78, 128.05, 128.57, 130.93, 139.51, 145.17, 170.86; HRMS (ESI) calcd for C₁₅H₁₃ClN₂O [M + H]⁺ 273.0789, found [M + H]⁺ 273.0790.

5-(3-Chlorophenyl)-1-phenylimidazolidin-2-one (5f). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.68; IR (ν cm⁻¹, CHCl₃): 1702, 3380 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.51 (t, J = 6.7 Hz, 2H), 4.59 (t, J = 6.6 Hz, 1H), 4.99 (s, 1H, NH), 6.65–6.73 (m, 3H), 7.09–7.39 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 44.01, 55.17, 117.62, 124.40, 126.68, 127.17, 127.67, 128.13, 129.10, 134.15, 139.12, 144.90, 171.27; HRMS (ESI) calcd for C₁₅H₁₃ClN₂O [M + H]⁺ 273.0789, found [M + H]⁺ 273.0789.

5-(4-Chlorophenyl)-1-phenylimidazolidin-2-one (5g). Brownish-yellow viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.67; IR (ν cm⁻¹, CHCl₃): 1704, 3384 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.48 (t, J = 6.1 Hz, 2H), 4.57 (t, J = 6.4 Hz, 1H), 4.97 (s, 1H, NH), 6.66–6.78 (m, 3H), 7.07–7.40 (m, 6H); ¹³C NMR (100 MHz, CDCl₃): δ 44.36, 57.31, 117.90, 126.14, 127.00, 127.90, 128.27, 129.13, 139.39, 141.70, 171.46; HRMS (ESI) calcd for C₁₅H₁₃ClN₂O [M + H]⁺ 273.0789, found [M + H]⁺ 273.0786.

5-(Furan-2-yl)-1-phenylimidazolidin-2-one (5h). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.63; IR (ν cm⁻¹, CHCl₃): 1702, 3384 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.55 (t, J = 6.5 Hz, 2H), 4.48 (t, J = 6.8 Hz, 1H), 4.94 (s, 1H, NH), 6.36–6.45 (m, 4H), 6.96–7.24 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 49.95, 60.41, 117.80, 126.73, 127.56, 128.63, 128.91, 140.25, 142.98, 151.09, 171.15; HRMS (ESI) calcd for C₁₃H₁₂N₂O₂ [M + H]⁺ 229.0972, found [M + H]⁺ 229.0974.

1-Phenyl-5-(thiphen-2-yl)imidazolidin-2-one (5i). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.64; IR (ν cm⁻¹, CHCl₃): 1704, 3382 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 3.69 (t, J = 6.4 Hz, 2H), 4.47 (t, J = 6.6 Hz, 1H), 5.02 (s, 1H, NH), 6.93–6.95 (m, 1H), 7.12–7.52 (m, 7H); ¹³C NMR (100 MHz, CDCl₃): δ 48.66, 61.85, 117.63, 127.71, 128.45, 129.06, 129.46, 129.91, 130.07, 139.13, 170.04; HRMS (ESI) calcd for C₁₃H₁₂N₂OS [M + H]⁺ 245.0743, found [M + H]⁺ 245.0740.

1-Ethyl-5-phenylimidazolidin-2-one (5j). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.66; IR (ν cm⁻¹, CHCl₃): 1704, 3380 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 1.27 (t, J = 8.52 Hz, 3H), 2.39–2.42 (q, J = 7.8 Hz, 2H), 3.60 (t, J = 6.6 Hz, 2H), 4.38 (t, J = 7.6 Hz, 1H), 4.92 (s, 1H, NH), 6.81–6.97 (m, 3H), 7.09–7.17 (m, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 18.38, 44.95, 52.43, 58.66, 128.46, 128.60, 129.02, 130.27, 135.32, 172.82; HRMS (ESI) calcd for C₁₁H₁₄N₂O [M + H]⁺ 191.1156, found [M + H]⁺ 191.1155.

1-Cyclohexyl-5-phenylimidazolidin-2-one (5k). Brownish viscous liquid; R_f (20% CH₃COOEt/C₆H₁₄) 0.67; IR (ν cm⁻¹, CHCl₃): 1704, 3382 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ 0.83–1.08 (m, 3H), 1.11–1.28 (m, 4H), 1.64 (t, J = 1.4 Hz, 1H), 1.73 (d, J = 3.5 Hz, 3H), 3.69 (t, J = 6.4 Hz, 2H), 4.51 (t, J = 6.7 Hz, 1H), 4.93 (s, 1H, NH), 6.96–7.00 (m, 1H), 7.17–7.32 (m, 4H); ¹³C NMR (100 MHz, CDCl₃): δ 24.86, 25.66, 25.71, 28.44, 28.51, 52.76, 53.48, 62.97, 129.43, 129.86, 131.48, 132.19, 141.68, 171.62; HRMS (ESI) calcd for C₁₅H₂₀N₂O [M + H]⁺ 245.1575, found [M + H]⁺ 245.1574.

Acknowledgements

The authors are thankful to the University Grant Commission (UGC) New Delhi, for the financial assistance and Sophisticated Analytical Instrumentation Facility (SAIF) Punjab University, Chandigarh for spectral analysis. R. Badru is thankful to UGC, New Delhi for providing research fellowship (10-2(5)/2007(ii)-E.U.II).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c4ra08048c

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