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Synlett 2008(19): 3068-3072  
DOI: 10.1055/s-0028-1087350
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

N,N′-(Phenylmethylene)diacetamide Analogues as Economical and Efficient Ligands in Copper-Catalyzed Arylation of Aromatic Nitrogen-Containing Heterocycles

Jie-Ping Wan, Yun-Feng Chai, Jian-Mei Wu, Yuan-Jiang Pan*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
Fax: +86(571)87951629; e-Mail: cheyjpan@zju.edu.cn;
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Publication History

Received 20 June 2008
Publication Date:
12 November 2008 (online)

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Abstract

N,N′-(Phenylmethylene)diacetamide analogues which were simply prepared from the condensation reaction of an aldehyde with an amide or urea were found to be efficient ligands in copper-catalyzed coupling reaction of aryl halides with various azole nucleophiles. The newly developed ligand showed broad application scope in this conversion. Compounds including imidazoles, benzoimidazoles, pyrrole, indole, and benzotriazole were successfully arylated with diversified aromatic halides to give corresponding products in moderate to excellent yields.

Key words

N,N′-(phenylmethylene)diacetamide - economical - ligand - copper - arylation

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Preparation of Ligands L1a-c
Benzaldehyde (10 mmol) and the corresponding amide (20 mmol) were added to the vessel with 5 mL MeCN (5 mL), and TMSCl (30 mol%) was applied as catalyst. The mixture was refluxed for 8 h. The crude product precipitated from the solution. The analytical pure product was obtained in 94%, 78%, and 92% yield, respectively, by washing with MeCN (3 mL).
Ligand L1a: ¹H NMR (500 MHz, DMSO-d 6): δ = 8.50 (d,
2 H), 7.38-7.27 (m, 5 H), 6.52 (t, 1 H), 1.86 (s, 6 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 169.5, 141.5, 129.2, 128.4, 127.3, 58.2, 23.4. ESI-MS: m/z = 229 [M + Na]+.
Preparation of L2a-2c
Benzaldehyde (10 mmol) and substituted urea (20 mmol) were mixed with MeCN (5 mL) and stirred at r.t. for 5 h. The corresponding product were furnished in quantitative yield after removal of solvent.
Ligand L2a: ¹H NMR (500 MHz, DMSO-d 6): δ = 7.31 (s,
4 H), 7.24 (s, 1 H), 6.63 (d, 2 H), 6.17 (s, 1 H), 5.96 (s, 2 H), 2.55 (s, 6 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 158.6, 143.8, 129.0, 127.9, 127.0, 60.3, 27.2. ESI-MS: 259 [M + Na]+.
Preparation of L3
Paraformaldehyde (0.6 g) and acetamide (20 mmol) were mixed in MeCN (5 mL), the mixture was refluxed at 110 ˚C for 10 h to give L3 in 75% yield.
Ligand L3: ¹H NMR (500 MHz, DMSO-d 6): δ = 6.44 (t,
2 H), 5.94 (s, 2 H), 4.22 (t, 2 H), 2.53 (d, 6 H). ¹³C NMR (125 MHz, DMSO-d 6): δ = 159.8, 47.0, 27.4. ESI-MS: 183 [M + Na]+.
General Experimental Procedure for the Arylation of Azole
Azole (0.5 mmol), aromatic halide (0.5 mmol), CuI (10 mol%), ligand (10 mol%) and NaOMe (1 mmol) were located in a flask with DMSO (1.5 mL). The mixture was heated at the corresponding temperature for 12 h. The reaction mixture was filtrated by SiO2 and extracted with EtOAc (3 × 8 mL). The combined organic was concentrated and subjected to SiO2 column to give target products.
Compound 3j: mp 247-250 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.59 (d, 2 H), 7.52 (d, 2 H), 7.41-7.37 (m, 4 H), 7.27 (s, 1 H), 7.19 (s, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 139.7, 138.8, 136.8, 135.7, 132.3, 130.2, 128.8, 128.6, 122.4, 122.1, 118.6. ESI-MS: 299 [M + H]+.
Compound 4c(liquid): ¹H NMR (500 MHz, CDCl3): δ = 8.60-8.57 (m, 2 H), 8.06 (t, 1 H), 7.88-7.85 (m, 2 H), 7.55 (d, 1 H), 7.38-7.35 (m, 2 H), 7.29-7.26 (m, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 150.0, 149.6, 144.8, 141.5, 139.1, 132.3, 124.4, 123.5, 122.0, 120.8, 114.5, 112.8. ESI-MS: 196 [M + H]+.