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Article

Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation

by
Xiaojia Zhao
,
Jiong Zhang
,
Zeqin Zheng
and
Runsheng Xu
*
Department of Biology and Environment, Zhejiang A&F University, Shaoxing 311800, Zhejiang, China
*
Author to whom correspondence should be addressed.
Molecules 2017, 22(1), 53; https://doi.org/10.3390/molecules22010053
Submission received: 21 November 2016 / Revised: 22 December 2016 / Accepted: 28 December 2016 / Published: 30 December 2016
(This article belongs to the Collection Heterocyclic Compounds)
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Abstract

:
A tandem transformation of C-N coupling/C-H carbonylation has been developed for the synthesis of benzo-1,4-oxazepine pharmaceutically derivatives. Notably, this reaction was accomplished by various phenylamine with ally halides under carbon dioxide atmosphere employing 2-(2-dimethylamino-vinyl)-1H-inden-1-olcatalyzed. Furthermore, under the optimized conditions, various benzo-1,4-oxazepine derivatives were obtained in good yields. Finally, a plausible CuI/CuIII mechanism of C-N coupling/C-H carbonylation transformation was proposed.

1. Introduction

The heterocycle benzoxazepines are privileged scaffolds in natural biologically products [1,2,3,4], pharmaceutical chemistry [5,6] and functionalized materials [7,8,9,10]. As such, Sintamilv (I) is an efficient antidepressant [11]; H1 receptor antagonist (II) is a selective antihistaminic agent [12]; and Sintamil (III) is a benzoxazepine analogue (Scheme 1) [13]. Furthermore, the therapeutic applications of benzoxazepines are for the central nervous system, along with anti-breast cancer activity and inhibitors of HIV [14,15].
Currently, the challenge in organic synthesis is developing an efficient and eco-friendly protocol, especially in the area of drug discovery and natural products. Benzoxazepines are generally synthesized by condensation of 2-aryloxyethylamines with 2-formylbenzoic acid [16]. Others have also been synthesized from amides [17] and amino acids [18,19]. However, most of these methodologies are associated with several drawbacks, such as low synthetic efficiency and sensitivity. Thus, a remarkable gap remains in the search of economical synthesis methods. Tandem transformation is one of the most effective ways to achieve this goal. Considering the above points, herein we report the tandem reaction green protocol for the synthesis of benzo-1,4-oxazepine pharmaceutical derivatives.
The reaction conditions were screened based on a model reaction of phenylamine 1a and (1-chloro-vinyl)-benzene 2a (Table 1). The ligands were mainly based on the derivatives of 2-(2-dimethylamino-vinyl)-1H-inden-1-ol. It was discovered that ligand L1 was the ideal choice for this transformation (Entries 5–10). CuI exhibited superior catalytic efficiency over all other examined CuI catalysts (Entries 1–5), and Cs2CO3 turned out to be the proper base additive (Entries 11–12). Meanwhile, the reaction temperature was 100 °C (Entries 15–16).
With the optimal conditions established, the reaction scope was further investigated. A wide array of phenylamine 1 and ally halide 2 was subjected to this reaction in moderate to good yields (Table 2). Phenylamine derivatives bearing either an electron-withdrawing or electron-donating group reacted smoothly with 2. This transformation is applicable for para-substituted phenylamines. Chloroethylene bearing an electron-donating group showed better reactivity than those with an electron-withdrawing group (All the product spectrums, please see Supplementary Materials).
Interestingly, we found that 1-bromo-cyclohexene 4 has also been rapidly synthesized in good yields, and the results are summarized in Table 3. In addition, the reaction works well for both bearing electron-donating and electron-withdrawing groups.
On the basis of the above experimental results, we tentatively proposed a reaction mechanism as shown in Scheme 2. At the beginning, CuI activate 6 was been formed through copper iodide coordinating with ligand. Next, complex 6 reacted with vinyl halides by oxidative addition produced a CuIII complex 7. The complex 7 reacted with aniline obtained the key intermediate complex 8 [20,21]. Selective ortho-carbonylation of the phenylamine was determined by Complex 9. Through the reductive elimination of Complex 9, Complex 10 was obtained, which regenerates Complex 6 for the next catalytic cycle [22,23]. However, how the ligand promotes this transformation is a part of ongoing study.

2. Results and Discussion

Molecules 22 00053 i020
2-Phenyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3a): A mixture of phenylamine 1a (0.5 mmol, 46.5 mg), (1-chloro-vinyl)-benzene 2a (0.6 mmol, 83.4 mg), CuI (10 mol %, 9.5 mg), L1 (10 mol %, 20.1 mg) and Cs2CO3 (2 equiv., 325.8 mg) in DMSO (4 mL) was stirred in CO2 at 100 °C for 10 h. After completion of the reaction, the mixture was quenched with saturated salt water (10 mL); the solution was extracted with ethyl acetate (3 × 10 mL). The organic layers were combined and dried over sodium sulfate. The pure product was obtained by flash column chromatography on silica gel to afford 3a 96.8 mg in 81% yield. The spectroscopic data of all of the products are presented below. Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.63 (m, 1H), 7.43 (br, 1H), 7.08–7.43 (m, 8H), 5.07 (dd, J = 8.0, 5.7 Hz, 1H), 4.08 (dd, J = 12.3, 8.0 Hz, 1H), 3.96 (dd, J = 12.3, 5.6 Hz, 1H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.7, 139.1, 132.9, 130.3, 128.6, 127.5, 126.6, 117.8, 116.4, 109.1, 77.6, 60.2; EIMS (m/z): 239 [M+]; Anal. Calcd. for C15H13NO2: C, 75.30; H, 5.48; N, 5.85; Found: C, 75.62; H, 5.13; N, 5.68.
Molecules 22 00053 i021
2-p-Tolyl-2,3-dihydro-1H-benzo[e][1,4] xazepine-5-one (3b): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.61 (m, 1H), 7.44 (br, 1H), 7.04–7.31 (m, 7H), 5.07 (dd, J = 8.0, 5.7 Hz, 1H), 4.07 (dd, J = 12.3, 8.0 Hz, 1H), 3.95 (dd, J = 12.3, 5.7 Hz, 1H), 2.39 (s, 3H); 13C-NMR (100 MHz, CDCl3): 168.6, 147.8, 138.3, 135.3, 132.3, 130.5, 128.1, 127.6, 118.2, 115.9, 109.5, 77.5, 60.3, 25.2; EIMS (m/z): 253 [M+]; Anal. Calcd. for C16H15NO2: C, 75.87; H, 5.97; N, 5.53; Found: C, 75.50; H, 6.20; N, 5.88.
Molecules 22 00053 i022
2-(4-Chloro-phenyl)-2,3-dihydro-1H-benzo[e][1,4] xazepine-5-one (3c): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.64 (m, 1H), 7.47 (br, 1H), 7.07–7.48 (m, 7H), 5.08 (dd, J = 8.1, 5.6 Hz, 1H), 4.09 (dd, J = 12.3, 8.1 Hz, 1H), 3.95 (dd, J = 12.3, 5.6 Hz, 1H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.7, 139.3, 133.3, 132.4, 130.5, 128.6, 127.8, 118.4, 116.3, 110.1, 77.3, 60.9;EIMS (m/z): 273 [M+]; Anal. Calcd. for C15H12ClNO2: C, 65.82; H, 4.42; N, 5.12; Found: C, 65.51; H, 4.61; N, 5.33.
Molecules 22 00053 i023
2-Methyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3d): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.62 (m, 1H), 7.42 (br, 1H), 7.05–7.21 (m, 3H), 4.58 (dd, J = 12.3, 8.0 Hz, 1H), 3.96 (dd, J = 12.2, 5.6 Hz, 1H), 3.12–3.71 (m, 1H), 1.35 (d, J = 7.1 Hz, 3H); 13C-NMR (100 MHz, CDCl3): 168.2, 147.3, 132.8, 130.4, 118.7, 116.6, 109.7, 77.1, 53.1, 18.2; EIMS (m/z): 177.08 [M+]; Anal. Calcd. for C10H11NO2: C, 67.78; H, 6.26; N, 7.90; Found: C, 68.14; H, 6.55; N, 7.53.
Molecules 22 00053 i024
7-Chloro-2-phenyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3e): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.63 (m, 1H), 7.43 (br, 1H), 7.10–7.46 (m, 7H), 5.08 (dd, J = 8.1, 5.6 Hz, 1H), 4.10 (dd, J = 12.4, 8.1 Hz, 1H), 3.97 (dd, J = 12.4, 5.6 Hz, 1H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.4, 139.5, 133.2, 130.2, 128.7, 127.5, 126.8, 123.8, 115.4, 109.2, 77.5, 60.2; EIMS (m/z): 273 [M+]; Anal. Calcd. for C15H12ClNO2: C, 65.82; H, 4.42; N, 5.12; Found: C, 65.70; H, 4.61; N, 5.44.
Molecules 22 00053 i025
7-Chloro-2-p-tolyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3f): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.64 (m, 1H), 7.43 (br, 1H), 7.07–7.38 (m, 6H), 5.08 (dd, J = 8.1, 5.9 Hz, 1H), 4.10 (dd, J = 12.4, 8.1 Hz, 1H), 3.96 (dd, J = 12.4, 5.9 Hz, 1H), 2.40 (s, 3H); 13C-NMR (100 MHz, CDCl3): 168.2, 147.1, 139.2, 135.8, 133.4, 130.5, 128.7, 126.9, 123.5, 115.5, 109.3, 77.2, 60.4, 25.7; EIMS (m/z): 287.07 [M+]; Anal. Calcd. for C16H14ClNO2: C, 66.79; H, 4.90; N, 4.87; Found: C, 66.95; H, 4.63; N, 5.23.
Molecules 22 00053 i026
7-Chloro-2-(4-chloro-phenyl)-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3g): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.66 (m, 1H), 7.46 (br, 1H), 7.09–7.50 (m, 6H), 5.10 (dd, J = 8.2, 5.6 Hz, 1H), 4.11 (dd, J = 12.4, 8.2 Hz, 1H), 3.96 (dd, J = 12.4, 5.6 Hz, 1H); 13C-NMR (100 MHz, CDCl3): 168.2, 147.4, 139.6, 133.2, 131.8, 130.2, 128.9, 126.7, 123.8, 115.2, 109.6, 77.5, 60.3; EIMS (m/z): 307 [M+]; Anal. Calcd. for C15H11Cl2NO2: C, 58.46; H, 3.60; N, 4.55; Found: C, 58.23; H, 3.92; N, 4.67.
Molecules 22 00053 i027
7-Chloro-2-methyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3h): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.64 (m, 1H), 7.45 (br, 1H), 7.06–7.23 (m, 2H), 4.6 (dd, J = 12.2, 8.1 Hz, 1H), 3.98 (dd, J = 12.2, 5.6 Hz, 1H), 3.12–3.71 (m, 1H), 1.36 (d, J = 7.2 Hz, 3H); 13C-NMR (100 MHz, CDCl3): 168.5, 147.3, 133.1, 130.2, 123.1, 116.8, 109.3, 77.5, 53.4, 18.3; EIMS (m/z): 211 [M+]; Anal. Calcd. for C10H10ClNO2: C, 56.75; H, 4.76; N, 6.62; Found: C, 56.89; H, 5.18; N, 6.34.
Molecules 22 00053 i028
7-Methyl-2-phenyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3i): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.58 (m, 1H), 7.41 (br, 1H), 7.06–7.40 (m, 7H), 5.00 (dd, J = 8.0, 5.6 Hz, 1H), 4.06 (dd, J = 12.2, 8.0 Hz, 1H), 3.92 (dd, J = 12.2, 5.6 Hz, 1H), 2.40 (s, 3H). 13C-NMR (100 MHz, CDCl3): 168.5, 147.2, 139.4, 133.3, 130.8, 128.9, 127.7, 126.9, 126.2, 116.7, 109.3, 77.8, 60.3, 25.3; EIMS (m/z): 253 [M+]; Anal. Calcd. for C16H15NO2: C, 75.87; H, 5.97; N, 5.53; Found: C, 75.65; H, 6.28; N, 5.33.
Molecules 22 00053 i029
7-Methyl-2-p-tolyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3j): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.56 (m, 1H), 7.44 (br, 1H), 7.06–7.36 (m, 6H), 4.98 (dd, J = 7.9, 5.6 Hz, 1H), 4.02 (dd, J = 12.2, 7.9 Hz, 1H), 3.90 (dd, J = 12.2, 5.6 Hz, 1H), 2.39 (s, 6H); 13C-NMR (100 MHz, CDCl3): 168.2, 147.5, 138.3, 135.1, 132.4, 130.8, 128.8, 127.5, 126.2, 116.2, 109.1, 77.2, 60.5, 25.8, 25.3; EIMS (m/z): 267 [M+]; Anal. Calcd. for C17H17NO2: C, 76.38; H, 6.41; N, 5.24; Found: C, 76.69; H, 6.24; N, 5.53.
Molecules 22 00053 i030
2-(4-Chloro-phenyl)-7-methyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3k): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.60 (m, 1H), 7.47 (br, 1H), 7.06-7.44 (m, 6H), 5.08 (dd, J = 8.0, 5.7 Hz, 1H), 4.10 (dd, J = 12.2, 8.0 Hz, 1H), 3.98 (dd, J = 12.2, 5.7 Hz, 1H), 2.42 (s, 3H); 13C-NMR (100 MHz, CDCl3): 168.1, 147.5, 139.6, 133.5, 132.2, 131.1, 128.3, 127.5, 126.4, 115.7, 109.7, 77.4, 60.7, 25.4; EIMS (m/z): 287 [M+]; Anal. Calcd. for C16H14ClNO2: C, 66.79; H, 4.90; N, 4.87; Found: C, 67.09; H, 4.99; N, 4.54.
Molecules 22 00053 i031
2,7-Dimethyl-2,3-dihydro-1H-benzo[e][1,4] xazepine-5-one (3l): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.62 (m, 1H), 7.43 (br, 1H), 7.04–7.20 (m, 2H), 4.56 (dd, J = 12.2, 8.0 Hz, 1H), 3.93 (dd, J = 12.2, 5.4 Hz, 1H), 3.10–3.70 (m, 1H), 2.41 (s, 3H), 1.34 (d, J = 7.0 Hz, 3H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.1, 133.5, 130.9, 126.8, 115.8, 109.2, 77.5, 53.4, 25.3, 18.3; EIMS (m/z): 191 [M+]; Anal. Calcd. for C11H13NO2: C, 69.09; H, 6.85; N, 7.32; Found: C, 69.41; H, 6.55; N, 7.16.
Molecules 22 00053 i032
5a,6,7,8,9,9a-Hexahydro-5H-10-oxa-5-aza-dibenzo[a,d]cyclohepten-11-one (5a): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.60 (m, 1H), 7.48 (br, 1H), 7.02–7.39 (m, 3H), 4.22 (dd, J = 11.3, 3.4 Hz, 1H), 3.11 (dd, J = 11.3, 3.5 Hz, 1H), 1.61–1.93 (m, 4H), 1.43–1.52 (m, 4H); 13C-NMR (100 MHz, CDCl3): 168.2, 147.6, 132.6, 130.1, 118.2, 115.9, 108.8, 85.8, 56.1, 28.5, 27.6, 22.9, 21.7; EIMS (m/z): 217 [M+]; Anal. Calcd. for C13H15NO2: C, 71.87; H, 6.96; N, 6.45; Found: C, 71.72; H, 6.66; N, 6.73.
Molecules 22 00053 i033
2-Chloro-5a,6,7,8,9,9a-hexahydro-5H-10-oxa-5-aza-dibenzo[a,d]cyclohepten-11-one (5b): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.62 (m, 1H), 7.49 (br, 1H), 7.05–7.43 (m, 2H), 4.26 (dd, J = 11.3, 3.5 Hz, 1H), 3.11 (dd, J = 11.3, 3.7 Hz, 1H), 1.62–1.95 (m, 4H), 1.43–1.54 (m, 4H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.1, 133.1, 130.4, 122.5, 116.1, 108.2, 85.6, 56.5, 28.8, 27.2, 22.7, 21.5; EIMS (m/z): 251 [M+]; Anal. Calcd. for C13H14ClNO2: C, 62.03; H, 5.61; N, 5.56; Found: C, 62.19; H, 5.31; N, 5.34.
Molecules 22 00053 i034
2-Methyl-5a,6,7,8,9,9a-hexahydro-5H-10-oxa-5-aza-dibenzo[a,d]cyclohepten-11-one (5c): Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.58 (m, 1H), 7.46 (1H, br), 7.00–7.35 (m, 2H), 4.20 (dd, J = 11.2, 3.2 Hz, 1H), 3.09 (dd, J = 11.2, 3.4 Hz, 1H), 2.40 (s, 3H), 1.60–1.91 (m, 4H), 1.42–1.50 (m, 4H); 13C-NMR (100 MHz, CDCl3): 168.4, 147.3, 133.4, 130.8, 126.1, 116.1, 108.5, 85.4, 56.3, 28.7, 27.8, 22.8, 21.5; EIMS (m/z): 231 [M+]; Anal. Calcd. for C14H17NO2: C, 72.70; H, 7.41; N, 6.06; Found: C, 72.99; H, 7.28; N, 6.48.

3. Experimental Section

3.1. General Procedure for Preparation of L1–L6

Dimethylformamide dimethyl acetal (DMF-DMA) (10 mmol, 1.19 g) and 1-(1-hydroxy-1H-inden-2-yl)-ethanone (10 mmol, 1.74 g) were dissolved in p-xylene (5 mL). Additionally, the mixture was refluxed during a period of 5–12 h, during which time a yellow precipitate formed. The precipitate was filtered out and washed with petroleum ether three times. The solid was vacuum-dried, and 1.89 g (yield 94%) of a yellow solid were obtained, L1 2-(2-dimethylamino-vinyl)-1H-inden-1-ol. 1H-NMR (400 MHz, CDCl3): δ 7.23 (m, 2H), 7.17–7.07 (t, J = 8.0 Hz, 2H), 7.01–6.90 (t, J = 7.8 Hz, 1H), 6.60 (s, 1H), 6.07–6.05 (d, J = 12 Hz, 1H), 2.47 (s, 3H), 2.42 (s, 3H); 13C-NMR (100 MHz, CDCl3): δ 146.1, 141.2, 133.8, 130.2, 127.9, 126.9, 123.2,121.2, 120.6, 104.1, 75.4, 46.1, 38.6.

3.2. 2-Phenyl-2,3-dihydro-1H-benzo[e][1,4]oxazepin-5-one (3a)

A mixture of phenylamine 1a (0.5 mmol, 46.5 mg), (1-chloro-vinyl)-benzene 2a (0.6 mmol, 83.4 mg), CuI (10 mol %, 9.5 mg), L1 (10 mol %, 20.1 mg) and Cs2CO3 (2 equiv., 325.8 mg) in DMSO (4 mL) was stirred in CO2 at 100 °C for 10 h. After completion of the reaction, the mixture was quenched with saturated salt water (10 mL); the solution was extracted with ethyl acetate (3 × 10 mL). The organic layers were combined and dried over sodium sulfate. The pure product was obtained by flash column chromatography on silica gel to afford 3a 96.8 mg in 81% yield. The spectroscopic data of all of the products are represented below. Yellowish oil. 1H-NMR (400 MHz, CDCl3): 7.63 (m, 1H), 7.43 (br, 1H), 7.08–7.43 (m, 8H), 5.07 (dd, J = 8.0, 5.7 Hz, 1H), 4.08 (dd, J = 12.3, 8.0 Hz, 1H), 3.96 (dd, J = 12.3, 5.6 Hz, 1H); 13C-NMR (100 MHz, CDCl3): 168.3, 147.7, 139.1, 132.9, 130.3, 128.6, 127.5, 126.6, 117.8, 116.4, 109.1, 77.6, 60.2; EIMS (m/z): 239 [M+]; Anal. Calcd. for C15H13NO2: C, 75.30; H, 5.48; N, 5.85; Found: C, 75.62; H, 5.13; N, 5.68.

4. Conclusions

In conclusion, we have found a green protocol for the synthesis of benzo-1,4-oxazepine derivatives involving tandem transformation of C-N coupling/C-H carbonylation. The method was economically viable and relevant to green chemistry.

Supplementary Materials

Supplementary materials can be accessed at: https://www.mdpi.com/1420-3049/22/1/53 /s1.

Acknowledgments

This work was supported by the Natural Science Foundation of Zhejiang Province (No. LQ15B020004), Natural Science Foundation ZA & FU (No. 04251700011).

Author Contributions

R.S.X. designed the experiments; J.Z. and Z.Z. analyzed the data and wrote the paper; X.J.Z. performed the experiments.

Conflicts of Interest

The authors declare no conflict of interest.

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  • Sample Availability: Samples of the compounds are available from the authors.
Molecules 22 00053 sch001 550
Scheme 1. The important benzo-1,4-oxazepine derivatives.
Scheme 1. The important benzo-1,4-oxazepine derivatives.
Molecules 22 00053 sch001
Molecules 22 00053 sch002 550
Scheme 2. A plausible mechanism of the catalytic cycle.
Scheme 2. A plausible mechanism of the catalytic cycle.
Molecules 22 00053 sch002
Table
Table 1. Optimization of the reaction conditions a.
Table 1. Optimization of the reaction conditions a.
Molecules 22 00053 i001
EntryLigandCu SaltBaseYield (%) b
1L1Cu(OAc)2Cs2CO38
2L1CuSO4Cs2CO30
3L1CuBrCs2CO323
4L1CuBr2Cs2CO319
5L1CuICs2CO381
6L2CuICs2CO329
7L3CuICs2CO336
8L4CuICs2CO347
9L5CuICs2CO316
10L6CuICs2CO338
11L1CuIK2CO342
12L1CuIK3PO40
13L1CuICs2CO361 c
14L1CuICs2CO369 d
Molecules 22 00053 i002
a Unless otherwise noted, reactions conditions were 1a (0.5 mmol), 2a (0.6 mmol), Cu salt (10 mol %), ligand (10 mol %), base (2 eq.), DMSO (4 mL) reacted in CO2 at 100 °C for 12 h; b isolated yield; c reaction under 90 °C; d reaction under 110 °C.
Table
Table 2. Synthesis of benzo-1,4-oxazepin-5-one 3 a.
Table 2. Synthesis of benzo-1,4-oxazepin-5-one 3 a.
Molecules 22 00053 i003
EntryR1R2Product 3Yield (%) b
1HPhMolecules 22 00053 i00481
2H4-CH3C6H4Molecules 22 00053 i00578
3H4-ClC6H4Molecules 22 00053 i00685
4HCH3Molecules 22 00053 i00774
54-ClPhMolecules 22 00053 i00879
64-Cl4-CH3C6H4Molecules 22 00053 i00976
74-Cl4-ClC6H4Molecules 22 00053 i01086
84-ClCH3Molecules 22 00053 i01184
94-CH3PhMolecules 22 00053 i01276
104-CH34-CH3C6H4Molecules 22 00053 i01375
114-CH34-ClC6H4Molecules 22 00053 i01482
124-CH3CH3Molecules 22 00053 i01572
a Reactions conditions were 1 (0.5 mmol), 2 (0.6 mmol), CuI (10 mol %), L1 (10 mol %), Cs2CO3 (2 equiv.), DMSO (4 mL) at 100 °C reacted in CO2 for 10 h; b isolated yield.
Table
Table 3. Synthesis of benzo-1,4-oxazepin-5-one 5 a.
Table 3. Synthesis of benzo-1,4-oxazepin-5-one 5 a.
Molecules 22 00053 i016
EntryR1Product 5Yield (%) b
1HMolecules 22 00053 i01778
24-ClMolecules 22 00053 i01884
34-CH3Molecules 22 00053 i01975
a Reactions conditions were 1 (0.5 mmol), 2 (0.6 mmol), CuI (10 mol %), L1 (10 mol %), Cs2CO3 (2 equiv.), DMSO (4 mL) at 100 °C reacted in CO2 for 10 h; b isolated yield.

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MDPI and ACS Style

Zhao, X.; Zhang, J.; Zheng, Z.; Xu, R. Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation. Molecules 2017, 22, 53. https://doi.org/10.3390/molecules22010053

AMA Style

Zhao X, Zhang J, Zheng Z, Xu R. Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation. Molecules. 2017; 22(1):53. https://doi.org/10.3390/molecules22010053

Chicago/Turabian Style

Zhao, Xiaojia, Jiong Zhang, Zeqin Zheng, and Runsheng Xu. 2017. "Facile Synthesis for Benzo-1,4-Oxazepine Derivatives by Tandem Transformation of C-N Coupling/C-H Carbonylation" Molecules 22, no. 1: 53. https://doi.org/10.3390/molecules22010053

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