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; Xiaoyan Li

doi:10.1055/s-0039-1691568

Synlett, Table of Contents

Synlett 2020; 31(04): 393-397
DOI: 10.1055/s-0039-1691568

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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

Abstract

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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.

Key words

dimethylamine - α-ketoamides - N-bromobutanimide - aryl methyl ketones - N,N-dimethylformamide

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References

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.

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