A simple direct phosgeneless route to N-heteroaryl unsymmetrical ureas

Abstract

A new simple approach to the synthesis of unsymmetrical ureas HetNC(O)NRR′ (HetNH = pyrrole, indole, carbazole; R, R′ = H, alkyl, aryl) has been explored, which involves the direct reaction of the N-phenoxycarbonyl derivatives of pyrrole, indole and carbazole, HetNCO₂Ph, with amines. The aminolysis reaction can be catalyzed by the amidine base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) under usually very mild conditions and provides a straightforward convenient entry into the target products through a route which avoids the traditional protocols based on multistep procedures and toxic phosgene or phosgene-derivatives.

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Introduction

The search for new direct eco-friendly synthetic routes is a major challenge for modern chemistry.¹ Despite the efforts currently devoted to redesign the synthesis of many classes of products according to strategies more sustainable from the environmental point of view, HetNC(O)NRR′ carboxamides of N-heteroarenes as pyrrole, indole and carbazole provide an example of chemicals which are still manufactured through traditional multistep methods based on risky and/or harmful starting materials. These particular unsymmetrical ureas,^2,3 wherein one of the ureidic N atoms is also part of a heteroaromatic ring,⁴ are widely used as synthetic intermediates,^5,6 find practical application in several fields,⁷ and usually exhibit biological activity or interesting pharmacological properties.^8,9

The classic methods of synthesis of these compounds start from derivatives of phosgene^4,10 or directly from COCl₂,^5,8 a toxic and harmful species, the utilization of which in chemical synthesis finds, nowadays, larger and larger constraints due to governmental policies for environmental protection.¹¹ The preliminary formation of a N-heteroaryl metal salt, HetNM, is often required. Usually, HetNC(O)NHR ureas are prepared by reaction of HetNM (M = Li, K, MgX) salts with isocyanates (Scheme 1(a)).^10a,b,dN,N-Disubstituted ureas HetNC(O)NRR′^4,5,8 have been often obtained by reaction of HetNM salts with N,N-disubstituted carbamoyl chlorides (Scheme 1(b)).⁴ A major additional problem of these approaches (Scheme 1) is also the regioselectivity of the electrophilic attack to the heterocyclic salt HetNM, which may depend on the nature of cation M and, therefore, necessitate the empirical characterization of the experimental conditions privileging N- over C-functionalization.¹²

Scheme 1 Classic phosgene-based synthetic routes to unsymmetrical ureas HetNC(O)NRR′.

A relatively more recent method (Scheme 2) used CO₂ as the source of carbonyl group and was based on the activation of carboxylic acid HetNCO₂H (HetNH = pyrrole, indole) to anhydride [HetNC(O)]₂O.¹³ However, the activation step requires the use of a stoichiometric amount of a coupling reagent as EDCI·HCl (1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride), usually manufactured from phosgene.¹⁴ Moreover, the synthetic route is atomically uneconomical, as it implies a multistep procedure and needs 2 mol of HetNH (for preforming the anhydride) per mol of product.

Scheme 2 Synthesis of unsymmetrical ureas HetNC(O)NRR′via HetNCO₂H activation.

In the last few years many efforts have been addressed to develop a fully phosgene-free chemistry and the study of safe non-toxic active carbonyl species which can serve as substitutes for phosgene or phosgene-derivatives has been drawing growing attention.^15–18 In this regard, carbonic acid diesters have been shown to play an important role^15a,16–18 as these compounds are currently manufactured, even on the industrial scale, through phosgene-free routes.^19,20 As a part of our studies in this field,^16,17 we have recently reported on the direct carbonylation of N-heteroaromatics HetNH, such as pyrrole, indole and carbazole, with organic carbonates for the phosgeneless synthesis of carbonyl derivatives HetNCO₂R,^17b,d usually obtained through phosgenation methods.²¹ The carbonylation reaction can be catalyzed by superbases as DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) or phosphazenes. Notably, the DBU-promoted reaction of HetNH (pyrrole, indole, carbazole) with diphenyl carbonate was shown to be an excellent new method for the selective high-yield synthesis of the N-phenoxycarbonyl derivatives HetNCO₂Ph 1–3 [eqn (1)].^17d Herein, with the intent of designing a fully phosgene-free green approach to the synthesis of unsymmetrical ureas HetNC(O)NRR′ (R, R′ = H, alkyl, aryl), we have explored the potential of compounds 1–3 as carbonylating agents of amines [eqn (2)]. Under usually mild conditions, the direct reaction of 1–3 with amines provided a straightforward phosgeneless access into N-heteroaryl unsymmetrical ureas HetNC(O)NRR′ (Fig. 1) through a convenient route which is an eco-friendly alternative to the classic methods described above.

Fig. 1 Synthesized unsymmetrical ureas.

Results and discussion

A preliminary study concerned the reaction of a primary aliphatic amine such as benzylamine with 1-phenoxycarbonyl pyrrole (1), which was selected as the reference substrate (Table 1). At 293 K, in the absence of any catalyst, 1 reacted promptly with an excess of benzylamine, used both as reactant and solvent, to afford 1-benzylaminocarbonyl pyrrole (4) and phenol: under the used solventless conditions (entry 1, Table 1), 1 was quantitatively converted into 4 within a short time (1 h). The formation of 4 was very selective (>99%). The attack of the amine to the substrate caused the selective expulsion of phenoxy group with formation of 4, which, under the working conditions, did not react further with the amine to generate the symmetrical urea (RNH)₂CO (R = benzyl). Accordingly, the IR spectrum of the reaction mixture in the range 1800–1600 cm⁻¹ showed one only absorption at 1701 cm⁻¹ due to 4.

Table 1 Aminolysis of C₄H₄NCO₂Ph (1) with PhCH₂NH₂, under different experimental conditions. The catalytic role of DBU

Entry	PhCH2NH2 (mmol)	1 (mmol)	DBU (mol%)^a	Solvent	T/K	t/h	Conversion^b [%]	4 [%]^c
a Relative to 1. b Of 1 (by GC). c Isolated yield (based on 1), unless otherwise specified. d 1 mL. e See also main text. f Selectivity to 4. g 2 mL.
1	5.95	1.07	—	—	293	1	100	86
2	0.66	0.59	—	Diethyl ether ^d	293	36^e	≈100	>99^f
3	1.24	1.10	100	Diethyl ether ^g	293	2	≈100	87
4	1.11	1.08	9.9	THF ^d	338	2	≈100	90

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Depending on the solvent properties and/or expensiveness of amine reactant, the use of solventless conditions, or a large excess of amine, may be poorly attractive from the synthetic point of view or not practicable at all. Therefore, the aminolysis reaction was studied also in ethereal solvents (diethyl ether or THF),²² using a modest excess of amine. In diethyl ether, at ambient temperature, the reaction of 1 with a slight excess (≈10 mol%) of PhCH₂NH₂ afforded 4 in practically quantitative yield (Entry 2, Table 1). However, under the used conditions, the conversion rate, while being satisfactory soon after mixing the reactants, became excessively slow in the long run (entry 2, Table 1) and the full conversion of the substrate required a markedly longer time.

The above behavior may reflect the fact that aminolysis of carbamates is usually catalyzed by amine itself, since a second molecule of amine can act as a catalyst of the process.²³ We have, therefore, investigated the effect of a base organo-catalyst and focused the attention on the strong amidine superbase DBU. Under experimental conditions otherwise analogous to those used in entry 2 (Table 1), the presence of 1 equivalent of the amidine superbase enhanced markedly the conversion rate (entry 3, Table 1). The aminolysis reaction was promoted also by markedly lower loadings of DBU, but less effectively, unless the working temperature was increased. Accordingly, at 338 K, in the presence of 10 mol% of DBU, 1 converted quantitatively to 4 within only 2 h (entry 4, Table 1).

Table 2 summarizes the results obtained with a few other amines. Like benzylamine, at ambient temperature also allylamine reacted easily with 1 (RNH₂/1 ≈ 1.14 mol/mol), in THF and in the presence of 1 equivalent of DBU, to afford 1-allylaminocarbonyl pyrrole (5) (entry 1, Table 2).

Table 2 Aminolysis of C₄H₄NCO₂Ph (1) to C₄H₄NC(O)NRR′ (R, R′ = H, alkyl, aryl) ureas by aliphatic or aromatic amines

Entry	amine (mmol)	1 (mmol)	DBU (mol%)^a	Solvent ^b	T/K	t/h	Conversion^c [%]	Urea: [%]^d
a Relative to 1. b 1 mL, when solvent (diethyl ether, THF) was used. c Of 1 (by GC). d Isolated yield (based on 1) of C4H4NC(O)NRR′, unless otherwise specified. e Selectivity. f The product formed in trace amounts. g After 8 days the conversion of 1 was close to 80%. h Not isolated. i After 4 days the conversion of 1 was close to 75%. j After 1 day the conversion of 1 was close to 70%.
1	CH2=CHCH2NH2 (0.94)	0.82	101	THF	293	2	100	5: 87
2	O(CH2CH2)2NH (0.63)	0.55	103	diethyl ether	293	2	100	6: >99^e
3	O(CH2CH2)2NH (1.20)	1.08	9.9	THF	338	2	100	6: 93
4	(PhCH2)2NH (1.20)	1.09	9.8	THF	338	6	≈ 0	7: ^f
5	(PhCH2)2NH (1.20)	1.09	9.8	THF	393	285	100^g	7: ^h
6	(PhCH2)2NH (0.62)	0.57	99.4	THF	393	166	99^i	7: ^h
7	(PhCH2)2NH (2.47)	0.82	10.0	—	423	18	99	7: ^h
8	(PhCH2)2NH (2.47)	0.82	102	—	423	5	100	7: ^h
9	(PhCH2)2NH (2.34)	0.74	202	—	293	60	100^j	7: 81
10	PhNH2 (5.49)	0.55	—	—	293	18	≈0	8: ^f
11	PhNH2 (5.49)	0.55	104	diethyl ether	293	48	99	8: 81
12	PhNH2 (2.47)	0.82	103	—	293	12	≈100	8: 83
13	PhNMeH (2.40)	0.81	108	—	293	38	≈100	9: 89
14	PhNMeH (2.49)	0.83	102	—	338	8	100	9: 88
15	PhNMeH (2.77)	0.85	10.2	—	373	48	99	9: 97^e

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The behavior of a few representative secondary aliphatic amines was also studied. In ethereal solvents (diethyl ether, THF) the DBU-promoted aminolysis of 1 with a cyclic secondary amine such as morpholine proceeded smoothly under very mild conditions and produced the relevant unsymmetrical urea 6 selectively (≥99%) with quantitative yield (entries 2 and 3, Table 2). In comparison, a sterically encumbered secondary acyclic amine, such as dibenzylamine, was, by far, much less reactive. For instance, under conditions similar to those used for morpholine in entry 3 (Table 2), dibenzylamine exhibited very poor reactivity towards 1 (entry 4, Table 1). Even at 393 K, the DBU-assisted aminolysis of 1 with a very modest excess of (PhCH₂)₂NH (≈10 mol% vs.1), in THF, required prohibitively long reaction times (entries 5 and 6, Table 2). Much higher conversion rates, which depended on the used catalyst load (10–100 mol%), were observed at higher temperature (423 K) under solventless conditions, using the amine in larger excess with respect to the substrate (entry 7 and entry 8, Table 2). In the range 393–423 K (entries 5–8, Table 2) the selectivity towards 1-dibenzylaminocarbonyl pyrrole (7) was moderate (≈75–85%) because of side-formation of other species, such as, for instance, phenyl N,N-dibenzylcarbamate (the major by-product)²⁴ and very minor amounts of 1,1′-carbonyldipyrrole.^17d The formation of significant amounts of (PhCH₂)₂NCO₂Ph demonstrates that, at these temperatures, the substitution of pyrryl moiety can seriously compete with that of phenoxy group. Higher selectivity to the target product 7 may be favored by markedly lower reaction temperatures. To overcome the consequent drawback due to the lower conversion rate a higher catalyst load was used. Accordingly, at 293 K, under solventless conditions, urea 7 was obtained selectively (≈99%) and quantitatively within a still reasonable reaction time (60 h) by reacting 1 with (PhCH₂)₂NH (amine/1 ≈ 3 mol/mol) in the presence 2 equivalent of DBU (entry 9, Table 2).

Under those conditions wherein benzylamine reacted readily with 1 in the absence of DBU (entry 1, Table 1), a primary aromatic amine such as aniline was practically inert towards 1 (entry 10, Table 2). The presence of DBU (1 equivalent vs.1) in the reaction mixture promoted the aminolysis of 1 with formation of 1-phenylaminocarbonyl pyrrole (8) even at ambient temperature (entries 11 and 12, Table 2). Under solventless conditions (entry 12, Table 2) the conversion rate was more satisfactory than in diethyl ether (entry 11, Table 2). The aminolysis reaction was promoted also by catalytic amounts of DBU, but, in this case, the quantitative conversion of 1 required a longer reaction time at ambient temperature. At 393 K (DBU = 10 mol% vs.1; PhNH₂/1 = 3 mol/mol), the conversion was faster, but less selective because of major formation of N,N′-diphenylurea, which, under the working conditions, formed by further reaction of 8 with aniline.^10a The analysis of the reaction mixture showed also the side-formation of trace amounts of 1,1′-carbonyldipyrrole.^17d

The synthetic protocol followed for aniline was extended also to N-methyl aniline (entries 13–15, Table 2) for the synthesis of 1-(N-methyl-N-phenylaminocarbonyl) pyrrole (9). The aminolysis reaction was selective (>96%) and, for instance, even at the highest temperature investigated (373 K; entry 15, Table 2), the side-formation of MePhNCO₂Ph was modest.

We have also explored the compatibility of the synthetic approach with the presence of a few functional groups in the molecule of amine and studied the ureidization of functionalized amines, such as the methyl ester of L-leucine, which we have used in the form of chlorohydrate salt, and a few amino alcohols (Table 3).

Table 3 Aminolysis of C₄H₄NCO₂Ph (1) with functionalized amines

Entry	amine reactant^a (mmol)	1 (mmol)	DBU (mol%)^b	THF (mL)	T/K	t/h	Conversion^c[%]	Urea: [%]^d
a R is Me2CHCH2CH(CO2Me). b Relative to 1. c Of 1 (by GC). d Isolated yield (based on 1), unless otherwise specified. e No reaction was observed. f Corresponding to 1 equivalent of DBU with respect to the chlorohydrate salt. g Not isolated. h Corresponding to 1.97 equivalents of DBU with respect to the chlorohydrate salt. i Corresponding to 1.81 equivalents of DBU with respect to the chlorohydrate salt. j Selectivity to 11. k After 36 h the conversion was nearly quantitative and addition of more AE (0.011 mL, 0.20 mmol) caused the fast conversion of the residual amounts of 1.
1	L-RNH3Cl (0.65)	0.49	—	1	293	46	^e	10: ^e
2	L-RNH3Cl (0.65)	0.49	131^f	3	293	24	<10	10: ^g
3	L-RNH3Cl (0.68)	0.55	246^h	3	293	44	≈100	10: 84
4	L-RNH3Cl (0.76)	0.60	229^i	3	333	16	≈100	10: 87
5	H2NCH2CH2OH (16.6)	0.75	—	—	293	1	100	11: ≈100^j
6	H2NCH2CH2OH (0.89)	0.56	—	1	293	2	≈100	11: ≈100^j
7	H2NCH2CH2OH (0.63)	0.58	—	1	293	36	^k	11: 85
8	H2NCH2CH2OH (0.64)	0.56	11.8	1	293	1	100	11: 81
9	H2NCH2CH(Ph)OH (0.99)	0.60	—	1	293	2	100	12: 91
10	H2NCH2CH(Ph)OH (0.79)	0.64	10.4	1	293	2	≈100	12: 80
11	H2NCH2CH(Ph)OH (0.67)	0.58	100.5	1	293	0.25	100	12: 78

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At 293 K, the salt L-Me₂CHCH₂CH(CO₂Me)NH₃Cl (L-RNH₃Cl) was poorly reactive towards 1 (entry 1, Table 3) because of poor nucleophilicity of quaternary N atom. A negligible conversion to urea 10 was observed also when the substrate and the salt were reacted at ambient temperature in the presence of 1 equivalent (vs the salt) of the amidine base (entry 2, Table 3), which, under the working conditions, acted mainly as a proton scavenger [eqn (3)]²⁵ rather than as the catalyst. The aminolysis of 1 by the chlorohydrate salt required a larger amount of the amidine base and, under very mild temperature conditions (293–333 K), was achieved more effectively by working in the presence of ≈2 equivalents of DBU (vs the salt; entry 3 and entry 4, Table 3).²⁸

Me₂CHCH₂CH(CO₂Me)NH₃Cl + DBU ⇄ DBU·HCl + Me₂CHCH₂CH(CO₂Me)NH₂ (3)

In principle, the reaction of 1 with aminoalcohols H₂N-R-OH may effect not only the functionalization of H₂N-moiety but also that of OH group with formation of carbamate C₄H₄NC(O)O-R-NH₂. Elsewhere, in fact, we have reported that 1 can react with alcohols through a transesterification reaction.^17dMethanol reacted easily with 1, even at ambient temperature, to give 1-methoxycarbonyl pyrrole, C₄H₄NCO₂Me, but more sterically crowded alcohols, as PhCH₂OH or t-BuOH, required the use of higher temperatures and/or a catalyst as DBU. In the presence of DBU the transesterification process was less selective, as the amidine base can also cause the defunctionalization of the heteroaromatic ring with formation of pyrrole and carbonic acid diesters (ROC(O)OPh, (RO)₂CO).^17b,d

We have found that, in THF, in the presence of DBU (10-100 mol% vs.1), 1 reacted smoothly with aminoalcohols H₂N-R-OH (H₂N-R-OH/1 = 1.14–1.20 mol/mol) such as 2-aminoethanol (AE) or (±)-2-amino-1-phenylethanol (Ph-AE) to give, under very mild conditions (293 K), the corresponding ureas 11 and 12 with high yield (entries 8, 10 and 11, Table 3). However, variable amounts of C₄H₄NC(O)NHCH₂CHRO(O)CNC₄H₄ (17: R = H; 18: R = Ph) also formed under the working conditions (see also Experimental).

Scheme 3 shows two possible routes for the formation of C₄H₄NC(O)NHCH₂CHRO(O)CNC₄H₄, both of which, in principle, may be operative. However, we note that in no case we detected (by GC, GC-MS) the presence of C₄H₄NCO₂CHRCH₂NH₂ (R = H, Ph) in the reaction mixture. This fact suggests that C₄H₄NCO₂CHRCH₂NH₂, if it really formed, did not accumulate in the reaction mixture, but reacted fast to give C₄H₄NC(O)NHCH₂CHRO(O)CNC₄H₄.

Scheme 3 Possible routes to C₄H₄NC(O)NHCH₂CHRO(O)CNC₄H₄.

The selectivity towards the target products can be controlled more easily by working in the absence of the amidine base and suitably varying the H₂N-R-OH/1 molar ratio. For instance, only minor amounts of C₄H₄NC(O)NHCH₂CH₂O(O)CNC₄H₄ were detected in the reaction mixture when 1 was reacted with a slight excess of AE (AE/1 = 1.09 mol/mol; entry 7, Table 3), at 293 K, in THF. Under the above conditions most of substrate (≈90%) reacted within the first 4–5 h, but the conversion of the residual amounts of 1 required a longer time. The use of a higher H₂N-R-OH/1 molar ratio (60–65 mol%; entry 6 and 9 in Table 3) or of solventless conditions (entry 5, Table 3) allowed to overcome the above drawback and to conjugate high selectivity (≈100%) towards 11 or 12 with more satisfactory conversion rate.

Table 4 shows a few examples of aminolysis of 1-phenoxycarbonyl indole (2) and 9-phenoxycarbonyl carbazole (3). Under the working conditions (Table 4), the aminolysis of 3 with morpholine proceeded more sluggishly. Moreover, substrate 3 reacted with the investigated amines (allylamine, morpholine) with moderate selectivity (≈70%) mainly because of competitive defunctionalization of 3 and formation of carbazole (Scheme 4, route (b)). In comparison, the analogous reactions of 1 (see also Table 2) and 2 with the same amines were more selective and only in the aminolysis of 2 with morpholine (entry 3, Table 4) minor amounts of HetNH (indole) and O(CH₂CH₂)₂NCO₂Ph were found in the reaction mixture. The above features may reflect the importance of steric factors (bulkiness of both the attacking amine and HetN group in the substrate) in controlling not only the rate of the aminolysis process, but also the direction of the substitution reaction.

Table 4 DBU-promoted aminolysis of HetNCO₂Ph (2, 3) to HetNC(O)NRR′^a

Entry	Amine (mmol)	HetNCO2Ph (mmol)	Urea: [%]^b
a Solvent: THF (1 mL); DBU: ≈100 mol% vs.2 or 3; temperature: 293 K; reaction time: 3 h, except in entry 4 (10 h). Under the working conditions, the substrate (2 or 3) converted quantitatively or, if any, was detected in trace amounts. b Isolated yield (based on HetNCO2Ph) of HetNC(O)NRR′.
1	CH2=CHCH2NH2 (0.96)	2 (0.86)	13: 92
2	CH2=CHCH2NH2 (0.96)	3 (0.86)	14: 64
3	O(CH2CH2)2NH (0.80)	2 (0.71)	15: 92
4	O(CH2CH2)2NH (0.80)	3 (0.71)	16: 61

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Scheme 4 Aminolysis of HetNCO₂Ph.

Conclusion

The reaction of the N-phenoxycarbonyl derivatives of pyrrole, indole and carbazole, HetNCO₂Ph, with amines has been shown to be a convenient method of synthesis of unsymmetrical ureas HetNC(O)NRR′ (HetNH = pyrrole, indole, carbazole). The aminolysis reaction can be catalyzed by the amidine base DBU under usually mild conditions and proceeded with good to excellent selectivity depending on the working conditions (substrate, amine, temperature). The protocol has been successfully extended also to functionalized amines, such as amino esters and amino alcohols.

The synthetic approach is simple, direct, efficient and allows to gain access to the target products through a phosgene- and halogen-free synthetic pathway (Scheme 5; as a comparison, see also Scheme 1), which is safe and obviates the large co-generation of wastes (salts, etc.) typical of phosgenation methods. It provides a new solution for the synthesis of unsymmetrical ureas HetNC(O)NRR′ through a green route alternative to the current conventional procedures.

Scheme 5 Phosgeneless route to unsymmetrical ureas HetNC(O)NRR′.

Experimental

General methods

All solvents were dried according to conventional methods (P₂O₅; Na/benzophenone)²⁹ and stored under N₂. The carbonyl derivatives 1–3 were obtained as previously reported.^17dDBU and the amines were commercial products (Fluka or Aldrich) and were stored and manipulated under N₂ to prevent any significant contamination by atmospheric CO₂ and moisture. Ph-AE was purified by column chromatography (silica gel; MeOH as eluent) and recrystallized from EtOH(minimum amount)/diethyl ether/n-hexane before use. GC analyses were performed with a HP 5890 Series II gas-chromatograph (capillary column: Heliflex AT-5, 30 m × 0.25 mm, 0.25 μm film thickness). GC-MS analyses were carried out with a Shimadzu GC-17A linked to a Shimadzu GC-MS QP5050 selective mass detector (capillary column: Supelco MDN-5S, 30 m × 0.25 mm, 0.25 μm film thickness). IR spectra were taken on a Shimadzu FT-IR Prestige 21 spectrophotometer or recorded with a Perkin Elmer FT-IR 1710 instrument. Polarimetric measurements were carried out with a Perkin Elmer 343 Polarimeter. NMR spectra were run with a Varian Inova 400 spectrometer or a Bruker AM 500 instrument. Chemical shift are in δ (ppm) vs. Me₄Si. Coupling constants are in Hz.

Synthesis and characterization of unsymmetrical ureas HetNC(O)NRR′ (4–16)

The reactions were preferably conducted under N₂ and carried out in a ≈20 mL glass reactor equipped with a Sovirel cap and a Thorion stopcock.

1-Benzylaminocarbonyl pyrrole (N-benzyl-1H-pyrrole-1-carboxamide) 4. To the solution of 1 (0.2021 g, 1.08 mmol) in THF (1 mL), DBU (0.016 mL, 0.107 mmol) and the amine (0.130 mL, 1.11 mmol) were added (entry 4, Table 1). The reaction solution was stirred at 338 K for 2 h and, then, cooled to room temperature. Product 4 was isolated by column chromatography (silica gel; petroleum ether/diethyl ether (2 : 1 v/v)). Yield of 4: 194 mg, 90%. Found: C, 71.94; H, 6.09; N, 14.00. Calc. for C₁₂H₁₂N₂O: C, 71.98; H, 6.04; N, 13.98%; ν_max(Nujol)/cm⁻¹ 3321 s (NH), 1684vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 4.57 (2 H, d, J = 5.9, CH₂), 5.78 (1 H, br, NH), 6.25 (2 H, t, J = 2.2, H_β), 7.18 (2 H, t, J = 2.2, H_α), 7.26–7.38 (5 H, m, Ph); δ_C (100 MHz; CDCl₃; 293 K) 44.91 (CH₂), 111.99 (C_β), 118.38 (C_α), 127.88 (C_ortho), 127.91 (C_para), 128.87 (C_meta), 137.49 (C_ipso), 150.87 (C=O); m/z (EI) 200 (M⁺), 133 (M − C₄H₄NH), 104, 91, 67, 51, 39.

1-Allylaminocarbonyl pyrrole (N-(prop-2-en-1-yl)-1H-pyrrole-1-carboxamide) 5. The reaction mixture, prepared by adding DBU (0.125 mL, 0.84 mmol) and the amine (0.070 mL, 0.94 mmol) to the solution of 1 (0.1540 g, 0.82 mmol) in THF (1 mL), was stirred at 293 K for 2 h. Product 5 was isolated by column chromatography (silica gel; petroleum ether/diethyl ether (2 : 1 v/v)). Yield of 5: 107 mg, 87%. Found: C, 64.10; H, 6.73; N, 18.59. Calc. for C₈H₁₀N₂O: C, 63.99; H, 6.71; N, 18.65%; ν_max(Nujol)/cm⁻¹ 3333 s (NH), 1682vs (C=O); δ_H (500 MHz; CDCl₃; 293 K) 4.00 (2 H, tt, ³J_HCNH ≈ ³J_HCCH = 5.8, ⁴J = 1.5, CH₂), 5.18 (1 H, dq, ³J_cis = 10.3, ⁴J ≈ ²J = 1.4, H_cis), 5.24 (1 H, dq, ³J_trans = 17.2, ⁴J ≈ ²J = 1.4, H_trans), 5.76 (1 H, br, NH), 5.89 (1 H, m, HC=CH₂), 6.25 (2 H, t, J = 2.3, H_β), 7.19 (2 H, t, J = 2.3, H_α); δ_C (125 MHz; CDCl₃; 293 K) 43.21 (CH₂), 111.89 (C_β), 117.05 (CH = CH₂) 118.35 (C_α), 133.62 (HC = CH₂),150.84 (C=O); m/z (EI) 150 (M⁺), 135, 106, 94, 80, 67, 54, 41, 39.

1-Morpholinocarbonyl pyrrole (morpholin-4-yl(1H-pyrrol-1-yl)methanone) 6. To the solution of 1 (0.2012 g, 1.08 mmol) in THF (1 mL), DBU (0.016 mL, 0.107 mmol) and the amine (0.105 mL, 1.20 mmol) were added. The reaction solution was stirred at 338 K for 2 h, and, then, cooled to room temperature. Product 6 was isolated by column chromatography (silica gel; petroleum ether/diethyl ether (1 : 1 v/v)). Yield of 6: 180 mg, 93%. Found: C, 60.07; H, 6.80; N, 15.56. Calc. for C₉H₁₂N₂O₂: C, 59.99; H, 6.71; N, 15.54%; ν_max(Nujol)/cm⁻¹ 1682vs (C=O); δ_H (500 MHz; CDCl₃; 293 K) 3.60 (4 H, t, J = 4.8, NCH₂), 3.72 (4 H, t, OCH₂), 6.22 (2 H, t, J = 2.2, H_β), 6.98 (2 H, t, J = 2.3 Hz, H_α); δ_C (125 MHz; CDCl₃; 293 K) 46.98 (NCH₂), 66.56 (OCH₂), 110.98 (C_β), 120.33 (C_α), 153.88 (C=O); m/z (EI) 180 (M⁺), 149, 135, 122, 114 (M − C₄H₄N), 94, 80, 70, 66, 56, 42.

1-Dibenzylaminocarbonyl pyrrole (N,N-dibenzyl-1H-pyrrole-1-carboxamide) 7. To the mixture of 1 (0.139 g, 0.74 mmol) and the amine (0.450 mL, 2.34 mmol), DBU (0.225 mL, 1.51 mmol) was added (entry 9, Table 2). The reaction solution was stirred at 293 K for 60 h and, then, dissolved in diethyl ether (25 mL). The ethereal solution was washed with H₂O (2 × 25 mL), HCl 0.13 M (2 × 25 mL), again with H₂O, dried over MgSO₄ and evaporated in vacuo. Yield of 7: 174 mg, 81%. Product 7 can be recrystallized at 253 K from diethyl ether/n-hexane. Found: C, 78.63; H, 6.28; N, 9.61. Calc. for C₁₉H₁₈N₂O: C, 78.59; H, 6.25; N, 9.64%; ν_max(Nujol)/cm⁻¹ 1674vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 4.58 (4 H, s, CH₂), 6.21 (2 H, t, J = 2.2, H_β), 7.11 (2 H, t, J = 2.2, H_α), 7.23 (4 H, dm, H_ortho), 7.31 (2 H, m, H_para), 7.37 (4 H, m, H_meta); δ_C (100 MHz; CDCl₃; 293 K) 50.76 (CH₂), 111.02 (C_β), 120.59 (C_α), 127.73, 127.80, 128.88, 135.94 (C_ipso) 155.14 (C=O); m/z (EI) 290 (M⁺), 224 (M − C₄H₄N), 199 (M-PhCH₂), 156, 132, 104, 91, 77, 65, 51, 39.

1-Phenylaminocarbonyl pyrrole (N-phenyl-1H-pyrrole-1-carboxamide) 8. To the substrate 1 (0.1525 g, 0.82 mmol), DBU (0.125 mL, 0.837 mmol) and the amine (0.225 mL, 2.47 mmol) were added (entry 12, Table 2). The reaction mixture was stirred at 293 K for 12 h and, then, dissolved in diethyl ether (25 mL). The resulting solution was extracted with H₂O (2 × 20 mL) and the organic solvent was evaporated. The solid residue was washed with small volumes of H₂O and dried in vacuo. Yield of 8: 126 mg, 83%. Found: C, 70.93; H, 5.45; N, 15.01. Calc. for C₁₁H₁₀N₂O: C, 70.96; H, 5.41; N, 15.04%; ν_max(Nujol)/cm⁻¹ 3335 s (NH), 1690vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 6.31 (2 H, t, J = 2.2, H_β), 7.15 (1 H, m, H_para), 7.26 (1 H, br, NH), 7.28 (2 H, t, J = 2.2, H_α), 7.35 (2 H, m, H_meta), 7.48 (2 H, dm, H_ortho); δ_C (100 MHz; CDCl₃; 293 K) 112.51 (C_β), 118.53 (C_α), 120.41 (C_ortho), 124.91, (C_para), 129.22 (C_meta), 136.76 (C_ipso), 148.34 (C=O); m/z (EI) 186 (M⁺), 119 (M − C₄H₄NH), 91, 67, 51, 39.

1-(N-Methyl-N-phenylaminocarbonyl) pyrrole (N-methyl-N-phenyl-1H-pyrrole-1-carboxyamide) 9. To the substrate 1 (0.1509 g, 0.81 mmol), DBU (0.130 mL, 0.870 mmol) and the amine (0.260 mL, 2.40 mmol) were added (entry 13, Table 2). The reaction mixture was stirred at 293 K for 38 h and, then, dissolved in diethyl ether (10 mL). The resulting solution was washed with H₂O (20 mL), HCl 0.17 M (35 mL), NaOH 1 M (10 mL) and, again, with H₂O. The organic phase was dried on MgSO₄ and evaporated in vacuo. Yield of 9: 144 mg, 89%. Found: C, 71.93; H, 6.10; N, 13.97. Calc. for C₁₂H₁₂N₂O: C, 71.98; H, 6.04; N, 13.99%; ν_max(neat)/cm⁻¹ 1697vs and 1682vs (poorly resolved, C=O); δ_H (400 MHz; CDCl₃; 293 K) 3.44 (3 H, s, CH₃), 5.97 (2 H, t, J = 2.2, H_β), 6.74 (2 H, t, J = 2, H_α), 7.06 (2 H, dm, H_ortho), 7.21 (1 H, m, H_para), 7.31 (2 H, m, H_meta); δ_C (100 MHz; CDCl₃; 293 K) 40.11 (Me), 110.46 (C_β), 121.14 (C_α), 125.45 (C_ortho), 126.83 (C_para), 129.81 (C_meta), 144.48 (C_ipso), 152.97 (C=O); m/z (EI) 200 (M⁺), 134 (M − C₄H₄N), 119, 106, 77, 51, 39.

Methyl 4-methyl-2-[(1H-pyrrol-1-ylcarbonyl)amino]pentanoate 10. To the mixture of 1 (0.1122 g, 0.60 mmol) and L-leucine methylester hydrochloride (0.1377 g, 0.76 mmol), the solvent (THF, 3 mL) and DBU (0.295 mL, 1.37 mmol) were added (entry 4, Table 3). The resulting suspension was stirred at 333 K for 16 h, cooled to room temperature and filtered to remove the precipitate (mainly DBU·HCl). The solvent was evaporated and the residue fractionated by flash chromatography on a silica gel column with a petroleum ether/diethyl ether mixture (4 : 1 and, then, 2 : 1 (v/v)). Yield of 10: 124 mg, 87%. The product can be recrystallized at 253 K from diethyl ether/n-hexane. Found: C, 60.61; H, 7.70; N, 11.68. Calc. for C₁₂H₁₈N₂O₃: C, 60.49; H, 7.61; N, 11.75%; ν_max(Nujol)/cm⁻¹ 3325 s (NH), 1744vs (CO₂Me), 1667vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 0.95 (3 H, d, ³J = 8, CH₃), 0.97 (3 H, d, ³J = 8, CH₃), 1.58–1.80 (3 H, overlapped multiplets, CH₂ and CHMe₂), 3.76 (3 H, s, OMe), 4.68 (1 H, td, ³J_HCCH = 5, ³J_HCCH ≈ ³J_HCNH = 8, CHCO₂Me), 5.79 (1 H, br d, ³J_HCNH = 8, NH), 6.25 (2 H, t, J = 2, H_β), 7.19 (2 H, t, J = 2, H_α); δ_C (100 MHz; CDCl₃; 293 K) 21.91 (Me), 22.78 (Me), 24.83 (CHMe₂), 41.79 (CH₂), 51.99 (CHCO₂Me), 52.57 (OMe), 112.11 (C_β), 118.42 (C_α), 150.43 (C=O), 173.38 (CO₂Me); m/z (EI) 238 (M⁺), 179 (M − CO₂Me), 163, 138, 112, 88, 67, 55, 41.

1-(2-Hydroxyethyl)aminocarbonyl pyrrole (N-(2-hydroxyethyl)-1H-pyrrole-1-carboxamide) 11. To the solution of 1 (0.1053 g, 0.56 mmol) in THF (1 mL), DBU (0.010 mL, 0.067 mmol) and the amino alcohol (0.036 mL, 0.64 mmol) were added (entry 8, Table 3). The reaction mixture was stirred at 293 K for about 1 h and, after evaporating the solventin vacuo, was fractionated on a silica gel column using diethyl ether as the eluent. Yield of 11: 70 mg, 81%.³⁰ The product can be recrystallized at 253 K from diethyl ether/n-hexane. Found: C, 54.61; H, 6.60; N, 18.10. Calc. for C₇H₁₀N₂O₂: C, 54.54; H, 6.54; N, 18.16%; ν_max(Nujol)/cm⁻¹ 3395 s and 3310 s, 1682vs (C=O), 1551vs; δ_H (400 MHz; CDCl₃; 293 K) 2.67 (1 H, br s, OH), 3.52 (2 H, q, ³J = 5, NCH₂), 3.77 (2 H, t, ³J = 5, CH₂O), 6.23 (2 H, t, J = 2, H_β), 6.26 (1 H, br, NH), 7.18 (2 H, t, J = 2.2, H_α); δ_C (100 MHz; CDCl₃; 293 K) 43.12 (NCH₂), 61.65 (CH₂OH), 112.00 (C_β), 118.39 (C_α), 151.73 (C=O); m/z (EI) 154 (M⁺), 136 (M − H₂O), 122 (M − MeOH), 106, 94, 80, 67, 56, 41.

1-(2-Hydroxy-2-phenylethyl)aminocarbonyl pyrrole (N-(2-hydroxy-2-phenylethyl)-1H-pyrrole-1-carboxamide) 12. To the solution of 1 (0.1205 g, 0.64 mmol) and Ph-AE (0.1053 g, 0.79 mmol) in THF (1 mL), DBU (0.010 mL, 0.067 mmol) was added (entry 10, Table 2). The reaction mixture was stirred at 293 K for 2 h and, after evaporating the solventin vacuo, was fractionated on a silica gel column using a petroleum ether/diethyl ether (1 : 1 v/v) mixture as the eluent. Yield of 12: 118.5 mg, 80%.³¹ The product can be recrystallized (colorless plates) at 253 K from diethyl ether/n-hexane. Found: C, 67.90; H, 6.20; N, 12.09. Calc. for C₁₃H₁₄N₂O₂: C, 67.81; H, 6.13; N, 12.16%; ν_max(Nujol)/cm⁻¹ 3294 s, 1674vs (C=O), 1558 ms; δ_H (400 MHz; CDCl₃; 293 K) 2.4 (1 H, very broad, OH), 3.42 (1 H, ddd, ²J = 13.9, ³J_HCCH = 8.4, ³J_HCNH = 4.4, CH₂), 3.82 (1 H, ddd, ²J = 13.9, ³J_HCCH = 3.5, ³J_HCNH = 7.3, CH₂), 4.92 (1 H, dd, ³J_HCCH = 3.5, ³J_HCCH = 8.3, CH), 5.99 (1 H, br, NH), 6.25 (2 H, t, J = 2, H_β), 7.16 (2 H, t, J = 2, H_α), 7.26–7.40 (5 H, m, Ph); δ_C (100 MHz; CDCl₃; 293 K) 48.02 (NCH₂), 73.27 (CHOH), 112.05 (C_β), 118.39 (C_α), 125.78, 128.24, 128.71, 141.20 (C_ipso), 151.49 (C=O); m/z (EI) 230 (M⁺), 213 (M − OH), 181, 156, 144, 124, 107, 94, 80, 67, 51, 39.

1-Allylaminocarbonyl indole (N-(prop-2-en-1-yl)-1H-indole-1-carboxamide) 13. To the solution of 2 (0.2042 g, 0.86 mmol) in THF (1 mL), DBU (0.130 mL, 0.870 mmol) and the amine (0.072 mL, 0.96 mmol) were added. The reaction mixture was stirred at 293 K for 3 h and, then, evaporated in vacuo. The residue was dissolved in diethyl ether and the solution extracted with H₂O. After drying over MgSO₄, the ethereal solution was evaporated in vacuo and the residue was fractionated on a silica gel column using a petroleum ether/diethyl ether (3 : 1 v/v) mixture as the eluent. Yield of 13: 158.6 mg, 92%. Product 13 can be recrystallized at 253 K from diethyl ether(minimum amount)/n-hexane. Found: C, 71.90; H, 6.10; N, 13.90. Calc. for C₁₂H₁₂N₂O: C, 71.98; H, 6.04; N, 13.98%; ν_max(Nujol)/cm⁻¹ 3356 ms (NH), 1682vs and 1666vs (poorly resolved, C=O), 1535vs; δ_H (400 MHz; CDCl₃; 293 K) 4.09 (2 H, tt, ³J_HCCH ≈ ³J_HCNH = 5.5, ⁴J = 1.5, CH₂), 5.21 (1 H, dq, J_cis = 10.2, ²J ≈ ⁴J = 1.5, H_cis), 5.30 (1 H, dq, J_trans = 17.2, ²J ≈ ⁴J = 1.5 Hz, H_trans), 5.65 (1 H, br, NH), 5.96 (1 H, m, CH), 6.61 (1 H, dd, ³J = 3.7, ⁴J = 1.1, 3-H), 7.21 (1 H, m, ³J_5,4 = 7.7, ³J_5,6 = 7.3, ⁴J_5,7 = 1.1, 5-H), 7.30 (1 H, m, ³J_6,5 = 7.3, ³J_6,7 = 8.1, ⁴J_6,4 = 1.5, 6-H), 7.44 (1 H, d, ³J = 3.7, 2-H), 7.58 (1 H, dt, ³J_4,5 = 7.7, ⁴J_4,6 ≈ ⁴J_4,3 = 1.5, 4-H), 8.06 (1 H, dm, ³J_7,6 = 8, 7-H); δ_C (100 MHz; CDCl₃; 293 K) 43.28 (CH₂), 107.13, 114.01, 117.15, 121.22, 122.29, 123.96, 124.22, 130.17, 133.77, 135.03, 151.90 (C=O); m/z (EI) 200 (M⁺), 130, 117, 89, 65, 63, 41, 39.

9-Allylaminocarbonyl carbazole (N-(prop-2-en-1-yl)-9H-carbazole-9-carboxamide) 14. To the solution of 3 (0.2465 g, 0.86 mmol) in THF (1 mL), DBU (0.130 mL, 0.870 mmol) and the amine (0.072 mL, 0.96 mmol) were added. The reaction mixture was stirred at 293 K for 3 h and, then, evaporated in vacuo. The residue was dissolved in diethyl ether and the solution extracted with H₂O. After drying over MgSO₄, the ethereal solution was evaporated in vacuo and the residue was fractionated on a silica gel column using a petroleum ether/diethyl ether (10 : 1 v/v) mixture as the eluent. Yield of 14: 137.4 mg, 64%. The product can be recrystallized (colorless needles) at 253 K from diethyl ether(minimum amount)/n-hexane. Found: C, 76.85; H, 5.7; N, 11.09. Calc. for C₁₆H₁₄N₂O: C, 76.78; H, 5.64; N, 11.19%; ν_max(Nujol)/cm⁻¹ 3271 ms (NH), 1667vs (C=O), 1528vs; δ_H (400 MHz; CDCl₃; 293 K) 4.18 (2 H, tt, ³J_HCCH ≈ ³J_HCNH = 6, ⁴J = 1.5, CH₂), 5.25 (1 H, dq, J_cis = 10.3, ²J ≈ ⁴J = 1.5 Hz, H_cis), 5.34 (1 H, dq, J_trans = 17.2, ²J ≈ ⁴J = 1.5, H_trans), 5.77 (1 H, br, NH), 6.03 (1 H, m, CH), 7.33 (2 H, m), 7.47 (2 H, m), 8.02 (4 H, overlapped dm); δ_C (100 MHz; CDCl₃; 293 K) 43.45 (CH₂), 113.54, 117.43, 120.20, 122.29, 125.10, 126.95, 133.71, 138.27, 152.63 (C=O); m/z (EI) 250 (M⁺), 167, 140, 115, 113, 83, 63, 56, 41.

1-Morpholinocarbonyl indole ((1H-indol-1-yl)(morpholin-4-yl)methanone) 15. To the solution of 2 (0.1673 g, 0.71 mmol) in THF (1 mL), DBU (0.105 mL, 0.703 mmol) and the amine (0.070 mL, 0.80 mmol) were added. The reaction mixture was stirred at 293 K for 3 h and, then, evaporated in vacuo. The residue was fractionated on a silica gel column using a petroleum ether/diethyl ether (1 : 1 v/v) mixture as the eluent. The fractions containing the product were collected and the solvent was evaporated. The product, which was contaminated by minor amounts of O(CH₂CH₂)₂NCO₂Ph, was recrystallized at 253 K from diethyl ether/n-hexane. Yield of 15: 149.3 mg, 92%. Found: C, 67.90; H, 6.20; N, 12.10. Calc. for C₁₃H₁₄N₂O₂: C, 67.81; H, 6.13; N, 12.16%; ν_max(Nujol)/cm⁻¹ 1682vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 3.59 (4 H, t, J = 4.7, NCH₂), 3.77 (4 H, t, J = 5 Hz, OCH₂), 6.60 (1 H, dd, ³J = 3.7, ⁴J = 1, 3-H), 7.19 (1 H, m, ³J_5,4 = 7.7, ³J_5,6 = 7.3, ⁴J_5,7 = 1.1, 5-H), 7.29 (1 H, m, ³J_6,5 = 7, ³J_6,7 = 8.4, ⁴J_6, 4 = 1.1, 6-H), 7.29 (1 H, d, ³J = 3.7, 2-H), 7.58 (1 H, dt, ³J_4,5 = 7.7, ⁴J_4, 6 ≈ ⁴J_4, 3 = 1, H-4), 7.67 (1 H, dm, ³J_7,6 = 8, 7-H); δ_C (100 MHz; CDCl₃; 293 K) 47.05 (NCH₂), 66.67 (OCH₂), 106.27, 113.17, 121.12, 122.05, 123.75, 126.10, 129.59, 135.15, 154.27 (C=O); m/z (EI) 230 (M⁺), 200, 144 (M − N(CH₂CH₂)₂O), 130, 114 (M − C₈H₆N), 103, 89, 70, 63, 42.

9-Morpholinocarbonyl carbazole ((9H-carbazol-9-yl)(morpholin-4-yl)methanone) 16. To the solution of 3 (0.2028 g, 0.71 mmol) in THF (1 mL), DBU (0.105 mL, 0.703 mmol) and the amine (0.070 mL, 0.80 mmol) were added. The reaction mixture was reacted at 293 K for 10 h. After evaporating the solventin vacuo, diethyl ether was added. The resulting solution was washed with H₂O, dried on MgSO₄ and fractionated on a silica gel column using a petroleum ether/diethyl ether (1 : 1 v/v) mixture as the eluent. The chromatographic separation allowed to recover pure carbazole and a mixture of O(CH₂CH₂)₂NCO₂Ph and the target urea, from which 16 was isolated (120.2 mg, 61%) by recrystallyzation at 253 K from diethyl ether with n-hexane. Found: C, 72.90; H, 5.80; N, 9.95. Calc. for C₁₇H₁₆N₂O₂: C, 72.84; H, 5.75; N, 9.99%; ν_max(Nujol)/cm⁻¹ 1666vs (C=O); δ_H (400 MHz; CDCl₃; 293 K) 3.60 (4 H, t, J = 4.8, NCH₂), 3.78 (4 H, t, J = 5, OCH₂), 7.31 (2 H, m), 7.46 (2 H, m), 7.65 (2 H, dm, J = 8.1), 8.02 (2 H, dm, J = 7.7); δ_C (100 MHz; CDCl₃; 293 K) 46.80 (NCH₂), 66.84 (OCH₂), 112.58, 120.24, 121.82, 124.48, 126.68, 138.44, 153.95 (C=O); m/z (EI) 280 (M⁺), 194 (M − N(CH₂CH₂)₂O), 180, 166 (M − OCN(CH₂CH₂)₂O), 140, 114, 89, 70, 56, 42.

Acknowledgements

Università degli Studi di Bari (Fondi di Ateneo) and Ministero dell'Istruzione, dell'Università e della Ricerca (PRIN 2008A7P7YJ_002) are acknowledged for financial support. The Authors thank Dr C. Cardellicchio (ICCOM-CNR, Bari) for polarimetric analyses.

Notes and references

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30. From the chromatographic separation we isolated an impure fraction mainly containing the side-product 17 characterized as C₄H₄NC(O)NHCH₂CH₂O(O)CNC₄H₄ on the basis of the NMR and mass spectra. δ_H (400 MHz; CDCl₃; 293 K) 3.77 (2 H, q, J = 5, NCH₂), 4.54 (2 H, t, J = 5, CH₂O), 6.24 (1 H, br unresolved t, NH), 6.25 (2 H, t, J = 2, H_β), 6.26 (2 H, t, J = 2, H_β), 7.18 (2 H, t, J = 2, H_α,ureidic), 7.25 (2 H, t, J = 2, H_α,carbamic); δ_C (100 MHz; CDCl₃; 293 K) 40.52 (NCH₂), 65.79 (CH₂O), 112.26 (C_β,ureidic), 113.05 (C_β,carbamic), 118.39 (C_α,ureidic), 120.09 (C_α,carbamic), 150.89 (C(O)O), 151.19 (C=O); m/z (EI) 247 (M⁺), 180 (M − C₄H₅N), 137, 111, 94, 80, 67, 42.
31. From the chromatographic separation we collected an impure fraction mainly containing the side-product 18 characterized as C₄H₄NC(O)NHCH₂CH(Ph)O(O)CNC₄H₄ on the basis of the NMR and mass spectra. δ_H (400 MHz; CDCl₃; 293 K) 3.90–3.96 (2 H, m, NCH₂), 5.95 (1 H, br unresolved t, NH), 6.07 (1 H, dd, J = 4, 8, OCH), 6.24 (2 H, t, J = 2 H_β,ureidic), 6.25 (2 H, t, J = 2, H_β,carbamic), 7.13 (2 H, t, J = 2, H_α,ureidic), 7.28 (2 H, t, J = 2, H_α,carbamic), 7.34–7.46 (5 H, m, Ph); δ_C (100 MHz; CDCl₃; 293 K) 45.98 (NCH₂), 77.88 (CH), 112.15 (C_β,ureidic), 113.01 (C_β,carbamic), 118.38 (C_α,ureidic), 120.15 (C_α,carbamic),126.36, 129.05, 129.18, 136.36 (C_ipso), 150.10 (C(O)O), 150.87 (C=O); m/z (EI) 323 (M⁺), 281, 256, 213, 184, 170, 156, 146, 128, 104, 94, 77, 68, 51, 39.

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