Yundong Wua,
Lei Guo*a,
Yuxuan Liub,
Jiannan Xiangb and
Jun Jiang*c
aSchool of Material and Chemical Engineering, Tongren University, Tongren 554300, China. E-mail: cqglei@163.com
bCollege of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China
cSchool of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China. E-mail: jiangjunhust@163.com
First published on 23rd April 2021
Amides are prevalent in nature and valuable functional compounds in agrochemical, pharmaceutical, and materials industries. In this work, we developed a selective and mild method for the synthesis of N-aryl amides. Starting from commercially available nitroarenes and acyl halides, N-aryl amides with good yields can be obtained in water. Especially in the process of transformation, Fe dust is the only reductant and additive, and the reaction can be easily performed on a large scale.
Entry | Variations from standard conditions | Yieldb |
---|---|---|
a All reactions were performed with nitrobenzene (1a, 0.25 mmol), acyl chloride (2a, 0.5 mmol), reductant (1 mmol) and solvent (1 mL), 36 h.b Isolated yield. | ||
1 | No variation | 88 |
2 | Zn (4 equiv.) instead of Fe | 45 |
3 | Al (4 equiv.) instead of Fe | 17 |
4 | Mg (4 equiv.) instead of Fe | 18 |
5 | 80 °C instead of 60 °C | 68 |
6 | 40 °C instead of 60 °C | 78 |
7 | NMP instead of H2O | 30 |
8 | DMF instead of H2O | 22 |
9 | Toluene instead of H2O | 11 |
10 | PhCl instead of H2O | 14 |
11 | EtOH instead of H2O | 45 |
12 | Fe (5 equiv.) instead of (4 equiv.) | 88 |
13 | Fe (3 equiv.) instead of (4 equiv.) | 55 |
14 | Absence of Fe | Trace |
15 | PhCOCl (2.5 equiv.) instead of (2 equiv.) | 87 |
16 | PhCOCl (1.5 equiv.) instead of (2 equiv.) | 59 |
The optimized reaction conditions were employed for the transamidation of nitroarenes (1a) with acyl chloride (2) (shown in Table 2). The reaction of nitrobenzene (1a) and benzoyl chloride (2a) efficiently offered 88% yield of 3aa in 36 h at 60 °C. Various acyl chlorides reacted smoothly with nitrobenzene to give the N-aryl amide products in medium to excellent yields. It was observed that benzoyl chlorides with electron donating substituents afforded the higher yields of corresponding products (3ab–3ad, 3ak). However, the yield of anilides with electron withdrawing substituents were reduced (3ae, 3ag–3aj). Notably, both isobutyryl chloride and cyclohexanecarbonyl chloride were proven to be effective to produce the desired products in medium yield (3af, 3al). However, when we used 4-nitrobenzoyl chloride (2n) or 2-nitrobenzoyl chloride (2m), no obvious reactions were observed. Moreover, benzoyl fluoride reacted with nitrobenzene to give 3aa in 56% yield (3aa).
Subsequently, various nitroarenes were reacted with benzoyl chloride (2a) as shown in Table 3. The reaction of 2a with 1-methyl-4-nitrobenzene, 1-methyl-3-nitrobenzene and 1-chloro-4-methyl-2-nitrobenzene gave the corresponding products, 3ba, 3ca and 3ga in good yields. The 1-chloro-4-nitrobenzene and 1-bromo-4-nitrobenzene also participated well in this reaction (3ea, 3fa). Meanwhile, this reaction is also tolerant of 1-chloro-4-methoxy-2-nitrobenzene and 1,4-dichloro-2-nitrobenzene, and the desired products 3ha and 3ia were produced in 78% and 64% yields. However, it was observed that nitromethane (1j) failed to produce desired N-methylbenzamide in practical yields.
To verify the practicality of the reaction, a scale–up reaction were carried out. Nitrobenzene (1a, 10 mmol) reacted with benzoyl chloride and Fe under standard conditions, and the expected product 3aa was obtained in 80% yield (Scheme 2).
A series of control experiments were carried out to gain some insights into the possible mechanism. When radical trapping reagents (TEMPO) was added to the reaction mixture, the transformation was inhibited, implying that the transformation might proceed via radical process (Scheme 3a). Lacking of BzCl in the reaction, there was no PhNH2 generated (Scheme 3b). Then, we usedsd nitrosobenzene as the reactant under the standard conditions and the product 3aa was obtained (Scheme 3c), but N-phenyl-hydroxylamine or azobenzene or N,N′-diphenylhydrazine could not react with benzoyl chloride to generate 3aa (Scheme 3d) suggesting that nitrosobenzene might be involved as an intermediate in the transformation. Finally, when the reaction was conducted under a nitrogen atmosphere, we got the product 3aa in 86% yield (Scheme 3e). We observed that the color of the mixtures changed from colourless to pale brown and some brown solid was generated. We added 1 mL HCl (1 M) to the reaction mixtures and the precipitation was disappeared followed by color changing from pale brown to pale yellow. So we speculated that ferric hydroxide was generated in the transformation. Finally, the reaction of 1a with carboxylic acid anhydride Bz2O could not produce 3aa under the standard conditions (Scheme 3f).
According to the aforementioned experimental results and literature reports,25 PhCOCl or PhCOF was activated by ferrous powder to produce a benzoyl radical (Scheme 4a). Then, the benzoyl radical reacted with nitrosoarene originating from the reduction of nitroarene by ferrous powder to form the N–C bond. Finally, the generated radical further transforms into the desired product 3 in the presence of Ferrous ion and water (Scheme 4b).
1H NMR (400 MHz, DMSO-d6) δ 10.31 (s, 1H), 8.01 (d, J = 7.2 Hz, 2H), 7.84 (d, J = 7.8 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.56 (t, J = 7.2 Hz, 2H), 7.39 (t, J = 7.2 Hz, 2H), 7.14 (t, J = 7.3 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 166.1, 139.7, 135.5, 132.4, 129.1, 128.9, 128.1, 124.1, 120.9.
1H NMR (400 MHz, DMSO-d6) δ 10.22 (s, 1H), 7.92 (d, J = 7.6 Hz, 2H), 7.83 (d, J = 7.6 Hz, 2H), 7.38 (t, J = 8.0 Hz, 4H), 7.12 (t, J = 7.0 Hz, 1H), 2.41 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 165.8, 142.0, 139.7, 132.6, 129.4, 129.0, 128.2, 124.0, 120.8, 21.5.
1H NMR (400 MHz, DMSO-d6) δ 10.28 (s, 1H), 7.86–7.78 (m, 4H), 7.44 (t, J = 7.2 Hz, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.13 (t, J = 7.2 Hz, 1H), 2.43 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 166.2, 139.7, 138.2, 135.5, 132.6, 129.1, 128.7, 128.6, 125.3, 124.1, 120.8, 21.4.
1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.4 Hz, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.38–7.31 (m, 4H), 7.12 (t, J = 7.2 Hz, 1H), 2.41 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 168.3, 139.8, 137.7, 135.6, 131.0, 130.1, 129.2, 127.7, 126.1, 124.0, 120.1, 19.8.
1H NMR (400 MHz, DMSO-d6) δ 10.46 (s, 1H), 8.00 (s, 2H), 7.86 (s, 1H), 7.79 (d, J = 7.8 Hz, 2H), 7.39 (t, J = 7.2 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 163.1, 139.1, 138.5, 134.7, 131.3, 129.1, 127.0, 124.6, 120.9.
HRMS (ESI) m/z calcd for C13H10Cl2NO [M + H]+: 266.0134, found 266.0135.
1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.30 (t, J = 7.4 Hz, 2H), 7.04 (t, J = 7.2 Hz, 1H), 2.65–2.58 (m, 1H), 1.12 (d, J = 6.8 Hz, 6H).
13C NMR (100 MHz, DMSO-d6) δ 175.7, 139.9, 129.1, 123.4, 119.5, 35.4, 20.0.
1H NMR (400 MHz, DMSO-d6) δ 10.31 (s, 1H), 8.07 (t, J = 6.6 Hz, 2H), 7.80 (t, J = 8.0 Hz, 2H), 7.40 (t, J = 8.0 Hz, 4H), 7.13 (t, J = 7.2 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 164.9, 164.5 (d, JC–F = 247 Hz), 139.5, 131.9 (d, JC–F = 3 Hz), 130.9 (d, JC–F = 9 Hz), 129.1, 124.2, 120.9, 115.8 (d, JC–F = 22 Hz).
1H NMR (400 MHz, DMSO-d6) δ 10.39 (s, 1H), 8.18 (s, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.83–7.79 (m, 3H), 7.52 (t, J = 7.8 Hz, 1H), 7.39 (t, J = 7.8 Hz, 2H), 7.14 (t, J = 7.4 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 164.4, 139.4, 137.6, 134.7, 131.1, 130.7, 129.1, 127.3, 124.4, 122.2, 120.9.
1H NMR (400 MHz, DMSO-d6) δ 10.36 (s, 1H), 8.02 (d, J = 7.8 Hz, 2H), 7.81 (d, J = 7.8 Hz, 2H), 7.63 (t, J = 7.8 Hz, 2H), 7.38 (t, J = 7.2 Hz, 2H), 7.14 (t, J = 7.0 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 164.9, 139.4, 136.9, 134.1, 130.1, 129.1, 128.9, 124.3, 120.9.
1H NMR (400 MHz, DMSO-d6) δ 10.58 (s, 1H), 8.00 (d, J = 6.8 Hz, 2H), 7.92 (d, J = 7.8 Hz, 2H), 7.25 (t, J = 7.2 Hz, 2H), 7.15 (t, J = 7.8 Hz, 2H), 7.05 (t, J = 7.0 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 160.0, 143.8, 137.6, 133.0 (q, JC–F = 26 Hz),129.7, 128.1, 126.9 (q, JC–F = 3 Hz), 125.0, 123.8 (q, JC–F = 271 Hz), 121.0.
1H NMR (400 MHz, DMSO-d6) δ = 10.17 (s, 1H), 7.93 (s, 1H), 7.75 (d, J = 7.6 Hz, 2H), 7.40–7.27 (m, 3H), 7.09 (t, J = 7.6 Hz, 1H), 6.70 (dd, J = 3.4, 1.8 Hz, 1H).
13C NMR (101 MHz, DMSO-d6) δ 156.7, 148.0, 146.1, 139.0, 129.1, 124.2, 120.8, 115.2, 112.6.
HRMS (ESI) m/z calcd for C11H10NO2 [M + H]+: 188.0712, found 188.0716.
1H NMR (400 MHz, DMSO-d6) δ = 9.78 (s, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.27 (t, J = 7.8 Hz, 2H), 7.00 (t, J = 7.5 Hz, 1H), 2.32 (t, J = 11.6 Hz, 1H), 1.78–1.73 (m, 4H), 1.67–1.63 (m, 1H), 1.45–1.38 (m, 2H), 1.27–1.23 (m, 3H).
13C NMR (101 MHz, DMSO-d6) δ 174.7, 140.0, 129.0, 123.3, 119.5, 45.3, 29.6, 25.7.
HRMS (ESI) m/z calcd for C13H18NO [M + H]+: 204.1388, found 204.1385.
1H NMR (400 MHz, DMSO-d6) δ10.23 (s, 1H), 7.99 (d, J = 7.2 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 7.0 Hz, 1H), 7.55 (t, J = 7.4 Hz, 2H), 7.19 (d, J = 8 Hz, 2H), 2.31 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 165.8, 137.1, 135.5, 133.1, 131.9, 129.5, 128.8, 128.1, 120.9, 21.0.
1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 7.99 (d, J = 7.2 Hz, 2H), 7.68 (s, 1H), 7.61 (t, J = 7.4 Hz, 2H), 7.55 (t, J = 7.4 Hz, 2H), 7.29–7.23 (m, 1H), 6.95 (d, J = 7.2 Hz, 1H), 2.34 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 166.0, 139.6, 138.2, 135.5, 132.0, 128.9, 128.8, 128.1, 124.8, 121.4, 118.0, 21.7.
1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.05 (d, J = 7.0 Hz, 2H), 7.64 (d, J = 6.8 Hz, 1H), 7.59 (d, J = 7.0 Hz, 2H), 7.41 (d, J = 6.8 Hz, 1H), 7.34 (t, J = 7.0 Hz, 1H), 7.28–7.23 (m, 2H), 2.30 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 165.8, 136.9, 135.0, 134.2, 132.0, 130.8, 128.9, 128.1, 127.1, 126.5, 18.4.
1H NMR (400 MHz, DMSO-d6) δ 10.44 (s, 1H), 8.00 (d, J = 7.2 Hz, 2H), 7.88 (d, J = 8.2 Hz, 2H), 7.63–7.59 (m, 1H), 7.56 (t, J = 7.2 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H).
13C NMR (100 MHz, DMSO-d6) δ 166.1, 138.7, 135.2, 132.2, 129.0, 128.9, 128.2, 127.8, 122.3.
1H NMR (400 MHz, DMSO-d6) δ 10.46 (s, 1H), 8.03 (d, J = 7.2 Hz, 2H), 7.87 (d, J = 8.8 Hz, 2H), 7.65 (t, J = 7.2 Hz, 1H), 7.62–7.56 (m, 4H).
13C NMR (100 MHz, DMSO-d6) δ 166.1, 139.1, 135.2, 132.2, 131.9, 128.9, 128.2, 122.7, 115.8.
1H NMR (400 MHz, DMSO-d6) δ 10.46 (s, 1H), 8.04 (d, J = 7.8 Hz, 2H), 7.67–7.62 (m, 1H), 7.57 (t, J = 6.8 Hz, 2H), 7.46 (t, J = 8.4 Hz, 2H), 7.14 (d, J = 8.2 Hz, 1H), 2.35 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 165.8, 137.5, 135.2, 134.5, 132.3, 129.6, 129.4, 129.0, 128.6, 128.1, 126.9, 20.9.
HRMS (ESI) m/z calcd for C14H13ClNO [M + H]+: 246.0680, found 246.0682.
1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.03 (d, J = 7.8 Hz, 2H), 7.64 (t, J = 7.0 Hz, 1H), 7.57 (t, J = 7.2 Hz, 2H), 7.48 (d, J = 8.8 Hz, 1H), 7.29 (s, 1H), 6.92 (d, J = 8.8 Hz, 1H),3.81 (s, 3H).
13C NMR (100 MHz, DMSO-d6) δ 165.8, 158.7, 136.3, 134.4, 132.4, 130.3, 129.0, 128.2, 120.9, 113.9, 113.5, 56.1.
HRMS (ESI) m/z calcd for C14H13ClNO2 [M + H]+: 262.0629, found 262.0626.
1H NMR (400 MHz, DMSO-d6) δ 10.19 (s, 1H), 8.02 (d, J = 7.5 Hz, 2H), 7.80 (s, 1H), 7.67–7.62 (m, 2H), 7.58 (t, J = 7.2 Hz, 2H), 7.41 (d, J = 8.4 Hz, 1H).
13C NMR (100 MHz, DMSO-d6) δ 165.9, 136.9, 134.1, 132.6, 131.9, 131.4, 129.0, 128.4, 128.2, 128.1, 127.6.
Footnote |
† Electronic supplementary information (ESI) available: 1H NMR and 13C NMR spectra of new compounds. See DOI: 10.1039/d0ra10868e |
This journal is © The Royal Society of Chemistry 2021 |