Synlett 2020; 31(04): 393-397
DOI: 10.1055/s-0039-1691568
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed Oxidative Synthesis of α-Ketoamides from Aryl Methyl Ketones and N-Bromobutanimide Using N,N-Dimethylformamide as Dimethylamine Source

Ying Wei
,
Yongxia Yan
Center for Molecular Systems and Organic Devices (CMSOD), Key Laboratory for Organic Electronics and Information Displays (KLOEID) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, P. R. of China   Email: iamywei@njupt.edu.cn
,
Xiaoyan Li
› Author Affiliations
The project was supported by the National Natural Science Foundation of China (Grant No. 21602111), the Synergetic Innovation Centre for Organic Electronics and Information Displays, and the Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM).
Further Information

Publication History

Received: 27 November 2019

Accepted after revision: 02 January 2020

Publication Date:
24 January 2020 (online)


Abstract

A novel and practical Cu(OAc)2-catalyzed oxidative synthesis of α-ketoamides from aryl methyl ketones and N-bromobutanimide (NBS) using N,N-dimethylformamide (DMF) as dimethylamine (HNMe2) source and solvent has been developed under mild conditions. DMF was used as a HNMe2 source and can be easily converted into HNMe2 by acid hydrolysis. The mechanistic studies indicate that Cu(OAc)2 plays a dual role in providing both catalyst and oxidant.

Supporting Information

 
  • References and Notes

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  • 28 General Procedure for the Preparation of α-Ketoamides 2 – Synthesis of Compound 2a To a solution of acetophenone (0.12 mL, 1.0 mmol) and Cu(OAc)2 (218 mg, 1.2 mmol) in DMF (2 mL). NBS (213 mg, 1.2 mmol) was then added to the flask in succession. The reaction mixture was stirred at 80 °C for 12 h. After the starting material 1a was consumed as indicated by TLC, the reaction mixture was poured into water and then extracted with CH2Cl2 (3 × 10 mL). The combined organic phase was washed with water (3 × 10 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, petroleum ether/ethyl acetate = 2:1) to give 2a (148 mg, 84%) as a white solid. N,N-Dimethyl-2-oxo-2-phenylacetamide (2a) Yellow solid-liquid mixtures (148 mg, 84%). 1H NMR (500 MHz, CDCl3): δ = 2.96 (s, 3 H), 3.12 (s, 3 H), 7.50–7.53 (t, J = 7.5 Hz, 2 H), 7.63–7.66 (t, J = 7.5 Hz, 1 H), 7.94–7.95 (t, J = 7.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 33.9, 37.0, 128.9, 129.6, 132.9, 134.7, 166.9, 191.7. MS: m/z calcd: 177.0; found: 178.1 [M + 1]+. Anal. Calcd for C10H11NO2: C, 67.78; H, 6.26; N, 7.90. Found: C, 67.69; H, 6.27; N, 7.89. 2-(4-Methoxyphenyl)-N,N-dimethyl-2-oxoacetamide (2b) Colourless oil (180 mg, 87%). 1H NMR (500 MHz, CDCl3): δ = 2.95 (s, 3 H), 3.11 (s, 3 H), 3.89 (s, 3 H), 6.96–6.98 (m, 2 H), 7.90–7.92 (m, 2H). 13C NMR (125 MHz, CDCl3): δ = 33.8, 37.0, 55.5, 114.2, 126.0, 132.0, 164.7, 167.2, 190.4. MS: m/z calcd: 207.0; found: 208.1 [M + 1]+. Anal. Calcd for C11H13NO3: C, 63.76; H, 6.32; N, 6.76. Found: C, 63.88; H, 6.33; N, 6.77. N,N-Dimethyl-2-oxo-2-(p-tolyl)acetamide (2c) Colourless oil (171 mg, 90%). 1H NMR (500 MHz, CDCl3): δ = 2.43 (s, 3 H), 2.95 (s, 3 H), 3.11 (s, 3 H), 7.30–7.31 (d, J = 8.0 Hz, 2 H), 7.83–7.84 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 21.8, 33.8, 37.0, 129.6, 129.7, 130.5, 145.9, 167.1, 191.5. MS: m/z calcd: 191.0; found: 192.4 [M + 1]+. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 69.00; H, 6.84; N, 7.31. N,N-Dimethyl-2-oxo-2-(o-tolyl)acetamide (2d) Solid-liquid mixtures (164 mg, 86%). 1H NMR (500 MHz, CDCl3): δ = 2.65 (s, 3 H), 2.96 (s, 3 H), 3.09 (s, 3 H), 7.25–7.31 (m, 2 H), 7.43–7.46 (t, J = 7.5 Hz, 1 H), 7.66–7.68 (d, J = 7.5 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 21.7, 33.9, 36.9, 126.1, 132.5, 132.6, 133.6, 141.4, 167.7, 193.6. MS: m/z calcd 191.0; found: 192.5 [M + 1]+. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 69.20; H, 6.86; N, 7.31. 2-(4-Bromophenyl)-N,N-dimethyl-2-oxoacetamide (2e) Solid-liquid mixtures (206 mg, 81%). 1H NMR (500 MHz, CDCl3): δ = 2.96 (s, 3 H), 3.12 (s, 3 H), 7.65–7.66 (d, J = 8.0 Hz, 2 H), 7.81–7.82 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 34.0, 37.0, 131.0, 131.9, 132.3, 132.6, 166.3, 190.5. MS: m/z calcd: 254.9; found: 256.7 [M + 1]+. Anal. Calcd for C10H10BrNO2: C, 46.90; H, 3.94; N, 5.47. Found: C, 47.00; H, 3.93; N, 5.48. 2-(4-Chlorophenyl)-N,N-dimethyl-2-oxoacetamide (2f) Solid-liquid mixtures (168 mg, 80%). 1H NMR (500 MHz, CDCl3): δ = 2.97 (s, 3 H), 3.12 (s, 3 H), 7.48–7.50 (d, J = 8.5 Hz, 2 H), 7.89–7.90 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 34.0, 37.0, 129.3, 130.9, 132.5, 141.2, 166.4, 190.2. MS: m/z calcd: 211.0; found: 212.3 [M + 1]+. Anal. Calcd for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62. Found: C, 56.82; H, 4.75; N, 6.61. N,N-Dimethyl-2-(4-nitrophenyl)-2-oxoacetamide (2g) Light yellow solid-liquid mixtures (175 mg, 79%). 1H NMR (500 MHz, CDCl3): δ = 3.01 (s, 3 H), 3.15 (s, 3 H), 8.14–8.16 (m, 2 H), 8.34–8.36 (d, J = 8.5 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 34.2, 37.0, 124.0, 130.7, 137.4, 151.0, 165.5, 189.2. MS: m/z calcd: 222.0; found: 223.4 [M + 1]+. Anal. Calcd for C10H10N2O4: C, 54.05; H, 4.54; N, 12.61. Found: C, 54.15; H, 4.55; N, 12.62. N,N-Dimethyl-2-(3-nitrophenyl)-2-oxoacetamide (2h) Light yellow solid-liquid mixtures (168 mg, 76%). 1H NMR (500 MHz, CDCl3): δ = 3.03 (s, 3 H), 3.17 (s, 3 H), 7.73–7.76 (t, J = 7.5 Hz, 1 H), 8.30–8.32 (d, J = 7.5 Hz, 1 H), 8.49–8.50 (d, J = 8.0 Hz, 1 H), 8.78 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 34.3, 37.0, 124.4, 128.6, 130.2, 134.4, 135.1, 148.4, 165.3, 188.6. MS: m/z calcd: 222.0; found: 223.2 [M + 1]+. Anal. Calcd for C10H10N2O4: C, 54.05; H, 4.54; N, 12.61. Found: C, 53.93; H, 4.53; N, 12.62. N,N-Dimethyl-2-(naphthalen-1-yl)-2-oxoacetamide (2i) Solid-liquid mixtures (183 mg, 81%). 1H NMR (500 MHz, CDCl3): δ = 3.00 (s, 3 H), 3.18 (s, 3 H), 7.56–7.59 (m, 1 H), 7.63–7.66 (m, 1 H), 7.88–7.90 (d, J = 8.5 Hz, 1 H), 7.93–7.98 (m, 2 H), 8.02–8.04 (m, 1 H), 8.43 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 34.0, 37.1, 123.5, 127.0, 127.8, 129.0, 129.3, 129.8, 130.3, 132.3, 132.9, 136.2, 167.1, 191.8. MS: m/z calcd: 227.0; found: 228.3 [M + 1]+. Anal. Calcd for C14H13NO2: C, 73.99; H, 5.77; N, 6.16. Found: C, 73.89; H, 5.78; N, 6.15. N,N-Dimethyl-2-oxo-2-(thiophen-2-yl)acetamide (2j) Light yellow oil (139 mg, 76%). 1H NMR (500 MHz, CDCl3): δ = 3.04 (s, 3 H), 3.10 (s, 3 H), 7.18–7.19 (t, J = 4.5 Hz, 1 H), 7.79–7.82 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 34.3, 37.2, 128.5, 136.1, 136.4, 140.2, 165.7, 183.4. MS: m/z calcd: 183.0; found: 184.5 [M + 1]+. Anal. Calcd for C8H9NO2S: C, 52.44; H, 4.95; N, 7.64. Found: C, 52.33; H, 4.94; N, 7.65. 2-(Furan-2-yl)-N,N-dimethyl-2-oxoacetamide (2k) Light yellow oil (120 mg, 72%). 1H NMR (500 MHz, CDCl3): δ = 3.04 (s, 3 H), 3.09 (s, 3 H), 6.61 (s, 1 H), 7.38 (s, 1 H), 7.72 (s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 34.5, 37.2, 112.8, 122.4, 148.7, 150.1, 165.3, 178.4. MS: m/z calcd: 167.0; found: 168.2 [M + 1]+. Anal. Calcd for C8H9NO3: C, 57.48; H, 5.43; N, 8.38. Found: C, 57.59; H, 5.42; N, 8.37. N,N-Diethyl-2-oxo-2-phenylacetamide (2m) Yellow solid-liquid mixtures (63 mg, 31%). 1H NMR (500 MHz, CDCl3): δ = 1.14–1.17 (m, 3 H), 1.28–1.30 (m, 3 H), 3.22–3.26 (m, 2 H), 3.54–3.59 (m, 2 H),7.49–7.52 (m, 2 H), 7.62–7.65 (m, 1 H), 7.93–7.95 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 12.8, 14.0, 38.7, 42.0, 128.9, 129.5, 133.1, 134.5, 166.6, 191.5. MS: m/z calcd: 205.1; found: 206.4 [M + 1]+. Anal. Calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.31; H, 7.36; N, 6.83.