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phenyl group of the bippyphos [9]. Belestkaya has reported that the electron poor ligand 3, 5-(CF3) 2-xantphos is more
effective than xantphos and requires lower catalyst loading and gives higher yields of products than xantphos [10]. An
attempt by the same group for the arylation of urea using a copper catalyst was unsuccessful [10]. There have been
many reports recently on the arylation of different compounds such as amines [8], amides [11], and hydrazides [12],
etc. using copper catalysts in the presence of suitable ligands. It accelerates a variety of synthetic transformations via
time and energy saving protocols. As a part of our program to synthesize different biologically active molecules using
copper catalyzed coupling reactions, we carried out the following investigations and preliminary results are given
below. We report a simple and mild copper catalyzed amidation of aryl halides with phenylurea.
1. Experimental
General procedure: A screw-capped tube was charged with phenylurea (1 mmol), aryl halide (1.2 mmol), K3PO4
(2 mmol), CuI (10 mol%), N,N0-dimethylethylenediamine (20 mol%) and DMF (3 mL) at room temperature. After
closing, the tube was heated to 85 8C for specified time, allowed to cool to room temperature and the resulting mixture
was extracted with ethyl acetate. The organic layers were washed with water, dried over anhydrous sodium sulfate and
concentrated in vacuo; the crude product was purified by column chromatography on silica gel using EtOAc–hexane
(1:2) as eluent to afford the coupled product. The identity and purity of the known products was confirmed by 1H and
13C NMR spectroscopic analysis, and the new products were fully characterized.
1
3-Diphenylurea (carbanilide) (Table 2, entry 1): White solid in 95% isolated yield. M.p. 237.5 8C; H NMR
(400 MHz, DMSO-d6): d 8.63 (s, 2H), 7.45 (d, 4H, J = 8.6, Hz), 7.27 (t, 4H, J = 7.9 Hz), 6.96 (t, 2H, J = 7.3 Hz). 13
C
NMR (101 MHz, DMSO-d6): d 151.9, 139.1, 128.2, 121.3, 117.7. HRMS (EI, m/z) calcd. for C13H12N2O (M+) 212.25,
found 212.21. N-(4-Nitrophenyl)-N0-phenyl-urea (Table 2, entry 5): Orange solid in 99% isolated yield. M.p. 210–
211 8C; 1H NMR (400 MHz, DMSO-d6): d 9.40 (s, 1H), 8.89 (s, 1H), 8.18 (d, 2H, J = 9.3 Hz), 7.68 (d, 2H, J = 9.3 Hz),
7.47 (d, 2H, J = 8.6 Hz), 7.30 (t, 2H, J = 7.9 Hz), 7.01 (t, 1H, J = 7.4 Hz). 13C NMR (101 MHz, DMSO-d6): d 151.3,
145.8, 140.4, 138.4, 128.3, 124.6, 122.0, 118.2, 117.0. HRMS (EI, m/z) calcd. for C13H11N2O3 (M+) 257.25, found
257.23. N-(1-Naphthalenyl)-N0-phenyl-urea (Table 2, entry 9): White solid in 85% isolated yield. M.p. 221–223 8C;
1H NMR (300 MHz, DMSO-d6): d 9.08 (s, 1H), 8.79 (s, 1H), 8.15 (d, 1H, J = 8.7 Hz), 8.05 (d, 1H, J = 7.6 Hz), 7.93 (d,
1H, J = 7.6 Hz), 7.45–7.72 (m, 6H), 7.32 (t, 2H, J = 7.9 Hz), 6.96–7.09 (m, 1H). 13C NMR (300 MHz, DMSO-d6): d
153.38, 140.23, 134.75, 134.16, 129.31, 128.88, 126.37, 126.33, 126.24, 126.14, 123.37, 122.30, 121.75, 118.57,
117.84. HRMS (EI, m/z) calcd. for C17H14N2O (M+) 262.31, found 262.34. N-(2-Pyridinyl)-N0-phenylurea (Table 2,
entry 18): White solid in 55% isolated yield. M.p. 186–188 8C; 1H NMR (400 MHz, DMSO-d6): d 10.49 (s, 1H), 9.42
(s, 1H), 8.27 (d, 1H, J = 3.9 Hz), 7.77–7.70 (m, 1H), 7.55–7.45 (m, 3H), 7.34–7.26 (m, 2H, J = 4.1, 11.7 Hz), 7.05–
6.97 (m, 2H). 13C NMR (101 MHz, DMSO-d6): d 152.2, 151.5, 146.3, 138.4, 138.0, 128.4, 122.0, 118.3, 117.0, 111.5.
HRMS (EI, m/z) calcd. for C12H11N3O (M+) 213.24, found 213.28. N-(4-Fluorophenyl)-N0-phenylurea (Table 2, entry
22): White solid in 23% isolated yield; M.p. 240–242 8C; 1H NMR (300 MHz, DMSO-d6): d 8.68 (s, 1H), 8.64 (s, 1H),
7.41–7.52 (m, 4H), 7.27 (t, 2H, J = 7.9 Hz), 7.06–7.17 (m, 2H), 6.92–7.01 (m, 1H). 13C NMR (300 MHz, DMSO-d6): d
159.35, 156.2, 153.07, 140.07, 136.45, 129.2, 122.28, 120.46, 118.69, 115.83. HRMS (EI, m/z) calcd. for C13H11FN2O
(M+) 230.24, found 230.22.
2. Results and discussion
To find the optimum conditions for the coupling of phenylurea with aryl halide, the N-arylation of phenylurea
(1 mmol) with 4-iodobenzene (1.2 mmol) was investigated with different solvents, bases and various ligands
(20 mol%) in the presence of CuI (10 mol%) at various temperatures for 24 h. Of the ligands tested, N,N0-
dimethylethylenediamine (DMEDA) (Table 1, entry 4), tetramethylethylenediamine (TMEDA) (Table 1, entry 1), 2,
4-pentanedione (Table 1, entry 5), 1, 2-ethanediol (Table 1, entry 2), 1, 10-phenanthroline (Table 1, entry 3), the former
proved to be the best ligand. Among the solvents examined, dioxane (Table 1, entry 8), toluene (Table 1, entry 7), DMF
(Table 1, entry 4), and THF (Table 1, entry 6), DMF was the most effective for the coupling reaction; in other solvent
yield was low. Reaction was done at higher temperature 100 8C (Table 1, entry 11), yield was low. Among the bases
examined, K3PO4 (Table 1, entry 4), Cs2CO3 (Table 1, entry 9) and t-BuONa (Table 1, entry 10), K3PO4 was suitable
base. As shown in Table 1, the reaction between phenylurea and iodobenzene gave an excellent yield of N,N0-
diphenylurea after 24 h (Table 1, entry 4).